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ProgramAbstracts

BNF2008

Liebenwalde

2 BNF2008

Final Colloquium

of the SFB 507

The Berlin Neuroscience Forum 2008 is sponsored byThe Berlin Neuroscience Forum 2008 is sponsored byThe Berlin Neuroscience Forum 2008 is sponsored byThe Berlin Neuroscience Forum 2008 is sponsored byThe Berlin Neuroscience Forum 2008 is sponsored by

Brainclincs DiagnosticsBrainclincs DiagnosticsBrainclincs DiagnosticsBrainclincs DiagnosticsBrainclincs DiagnosticsPPPPPAA LAA LAA LAA LAA Laboratories GmbHaboratories GmbHaboratories GmbHaboratories GmbHaboratories GmbH

Millipore BioscienceMillipore BioscienceMillipore BioscienceMillipore BioscienceMillipore Bioscience

The Berlin Neuroscience Forum 2008 is the final colloquium of theThe Berlin Neuroscience Forum 2008 is the final colloquium of theThe Berlin Neuroscience Forum 2008 is the final colloquium of theThe Berlin Neuroscience Forum 2008 is the final colloquium of theThe Berlin Neuroscience Forum 2008 is the final colloquium of theSFB 507 “The Role of Non-Neuronal Cells in CNS disease”SFB 507 “The Role of Non-Neuronal Cells in CNS disease”SFB 507 “The Role of Non-Neuronal Cells in CNS disease”SFB 507 “The Role of Non-Neuronal Cells in CNS disease”SFB 507 “The Role of Non-Neuronal Cells in CNS disease”

This meeting is a joint activity ofThis meeting is a joint activity ofThis meeting is a joint activity ofThis meeting is a joint activity ofThis meeting is a joint activity of

Berlin Neuroimaging Center

Berlin School of Mind and Brain

Bernstein Center for Computational Neuroscience

Clinical Research Unit „Molecular Mechanisms of Opioid Analgesia inInflammatory Pain“

Doctoral Research Program „Computational Neuroscience“

GRK „Cellular Mechanisms of Learning and Memory - Consolidation in theHippocampal Formation“

GRK „Functional Insect Science“

GRK „Neuropsychiatry und Psychology of Aging“

GRK „The Impact of Inflammation on Nervous System Function“

International Graduate Program „Medical Neuroscience“

NeuroCure: Towards a Better Outcome of Neurological Disorders

Research Unit „Conflicts as Signals in Cognitive Systems“

SFB „Theoretical Biology“

SFB „Developmental Disturbances in the Nervous System“

SFB “The Role of Non-Neuronal Cells in CNS disease”

SFB/TR “Mesial Temporal Lobe Epilepsies”

SFB/TR “The Brain as a Target of Inflammatory Processes“

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07TTTTTable of Contentsable of Contentsable of Contentsable of Contentsable of Contents

TTTTTable of Contentsable of Contentsable of Contentsable of Contentsable of Contents

Organization 4

General Information 5

Scientific Program 7

List of Poster Presentations 11

Abstracts of Lectures 21

Abstracts of Oral Presentations 23

Abstracts of Poster Presentations 29

Information on Berlin Neuroscience Programs 71

Keywords 87

Author Index 89

Address List 93

4 BNF2008

Final Colloquium

of the SFB 507

PPPPPoster Juryoster Juryoster Juryoster Juryoster JuryGabriel Curio

Jens DreierRosemarie Grantyn

Josef Priller

OrganizationOrganizationOrganizationOrganizationOrganization

PPPPProgram Committeerogram Committeerogram Committeerogram Committeerogram Committee

HomepageHomepageHomepageHomepageHomepage

Ingolf BlasigGabriel CurioUlrich DirnaglKarl Einhäupl

Uwe HeinemannIsabella Heuser

Helmut KettenmannReinhold Kliegl

Gary LewinRandolf MenzelRobert NitschJochen PflügerWerner SommerChristoph SteinWerner ReutterArno Villringer

Bernd WalzBertram Wiedenmann

Laurenz WiskottFrauke Zipp

http://bnf2008.glia.mdc-berlin.de

Prof. Dr. Helmut KettenmannMeino Alexandra Gibson/Annika Buchheister

Max-Delbrück-Centrum für Molekulare Medizin (MDC) Berlin-BuchZelluläre Neurowissenschaften

Robert-Rössle-Str. 1013092 Berlin

Tel.: +49 30 9406 3336, Fax: +49 30 9406 3819EMail: gibson@mdc-berlin.de, a.buchheister@mdc-berlin.de

OrganizationOrganizationOrganizationOrganizationOrganization

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General InformationGeneral InformationGeneral InformationGeneral InformationGeneral Information

General InformationGeneral InformationGeneral InformationGeneral InformationGeneral Information

Thursday, June 5, 2008

Thursday, June 5, 2008Friday, June 6, 2008Saturday, June 7, 2008

0160 90218506

Height : 120 cmWidth: 100 cm

PPPPPoster Session Ioster Session Ioster Session Ioster Session Ioster Session IPoster No. 1- 59Thursday, June 5, 2008Friday, June 6, 2008

!!! Posters must be removedimmediately after the postersession on Friday !!!

PPPPPoster Session IIoster Session IIoster Session IIoster Session IIoster Session IIPoster No. 60 - 110Friday, June 6, 2008Saturday, June 7, 2008

Invited SpeakersInvited SpeakersInvited SpeakersInvited SpeakersInvited Speakers

WWWWWelcome to Berlinelcome to Berlinelcome to Berlinelcome to Berlinelcome to BerlinPresentationsPresentationsPresentationsPresentationsPresentations

YYYYYoung Investigatoroung Investigatoroung Investigatoroung Investigatoroung InvestigatorPresentationsPresentationsPresentationsPresentationsPresentations

12.00 - 15.0012.00 - 15.0012.00 - 15.0012.00 - 15.0012.00 - 15.00

12.00 - 19.3012.00 - 19.3012.00 - 19.3012.00 - 19.3012.00 - 19.30 8.30 - 19.00 8.30 - 19.00 8.30 - 19.00 8.30 - 19.00 8.30 - 19.00 8.30 - 13.00 8.30 - 13.00 8.30 - 13.00 8.30 - 13.00 8.30 - 13.00

15.35 - 17.0015.35 - 17.0015.35 - 17.0015.35 - 17.0015.35 - 17.0010.00 - 11.0010.00 - 11.0010.00 - 11.0010.00 - 11.0010.00 - 11.00

16.00 – 17.3016.00 – 17.3016.00 – 17.3016.00 – 17.3016.00 – 17.3010.00 - 11.0010.00 - 11.0010.00 - 11.0010.00 - 11.0010.00 - 11.00

45 min (talk)15 min (disc.)

20 min (talk)10 min (disc.)

10 min (talk)5 min (disc.)

RegistrationRegistrationRegistrationRegistrationRegistration

Office HoursOffice HoursOffice HoursOffice HoursOffice Hours

Office PhoneOffice PhoneOffice PhoneOffice PhoneOffice Phone

PPPPPoster Boardsoster Boardsoster Boardsoster Boardsoster Boards

PPPPPoster Sessionsoster Sessionsoster Sessionsoster Sessionsoster Sessions

Duration of OralDuration of OralDuration of OralDuration of OralDuration of OralPresentationsPresentationsPresentationsPresentationsPresentations

6 BNF2008

Final Colloquium

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Scientific PScientific PScientific PScientific PScientific Programrogramrogramrogramrogram

12.00 – 14.3012.00 – 14.3012.00 – 14.3012.00 – 14.3012.00 – 14.30 Arrival and Registration

14.30 – 14.3514.30 – 14.3514.30 – 14.3514.30 – 14.3514.30 – 14.35 Welcome: Helmut K Helmut K Helmut K Helmut K Helmut Kettenmannettenmannettenmannettenmannettenmann

14.35 - 15.3514.35 - 15.3514.35 - 15.3514.35 - 15.3514.35 - 15.35 Lecture ILecture ILecture ILecture ILecture IChair:Chair:Chair:Chair:Chair: Isabella HeuserCarl DeisserothCarl DeisserothCarl DeisserothCarl DeisserothCarl DeisserothDepartment of Bioengineering, Department of Psychiatry,Stanford, USAOptogenetics: development and neuropsychiatry application

15.35 15.35 15.35 15.35 15.35 – 17.0017.0017.0017.0017.00 PPPPPoster Session I and Coffee Breakoster Session I and Coffee Breakoster Session I and Coffee Breakoster Session I and Coffee Breakoster Session I and Coffee Break

17.00 17.00 17.00 17.00 17.00 – 18.0018.0018.0018.0018.00 WWWWWelcome to Berlin Sessionelcome to Berlin Sessionelcome to Berlin Sessionelcome to Berlin Sessionelcome to Berlin SessionChair: Chair: Chair: Chair: Chair: Robert Nitsch

PPPPPeter Veter Veter Veter Veter VajkoczyajkoczyajkoczyajkoczyajkoczyCharité - Universitätsmedizin Berlin, CVK, Klinik fürNeurochirurgieAngiogenesis in malignant brain tumors

Felix WichmannFelix WichmannFelix WichmannFelix WichmannFelix WichmannTechnische Universität Berlin, FG ModellierungKognitiver ProzesseModelling of cognitive processes

18:00 – 19:0018:00 – 19:0018:00 – 19:0018:00 – 19:0018:00 – 19:00 Lecture IILecture IILecture IILecture IILecture IIChair: Chair: Chair: Chair: Chair: Bernhard RonacherUwe HombergUwe HombergUwe HombergUwe HombergUwe HombergFachbereich Biologie, Tierphysiologie, Philipps-Universität MarburgNeural mechanisms of sky compass orientation in aninsect

19.3019.3019.3019.3019.30 Dinner and Informal Get-togetherDinner and Informal Get-togetherDinner and Informal Get-togetherDinner and Informal Get-togetherDinner and Informal Get-together

ThursdayThursdayThursdayThursdayThursday, June 5, 2008, June 5, 2008, June 5, 2008, June 5, 2008, June 5, 2008

Scientific ProgramScientific ProgramScientific ProgramScientific ProgramScientific Program

8 BNF2008

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FFFFFridayridayridayridayriday, June 6, 2008, June 6, 2008, June 6, 2008, June 6, 2008, June 6, 2008

8.00 – 9.008.00 – 9.008.00 – 9.008.00 – 9.008.00 – 9.00 BreakfastBreakfastBreakfastBreakfastBreakfast

9.00 – 10.009.00 – 10.009.00 – 10.009.00 – 10.009.00 – 10.00 Lecture IIILecture IIILecture IIILecture IIILecture IIIChair: Chair: Chair: Chair: Chair: Arno VillringerPPPPPatrick Haggardatrick Haggardatrick Haggardatrick Haggardatrick HaggardUniversity College London, Institute of CognitiveNeuroscience & Department of Psychology, London, UKTouch, vision and mental body representation

10.00 – 11.0010.00 – 11.0010.00 – 11.0010.00 – 11.0010.00 – 11.00 PPPPPoster Session I and Coffee Breakoster Session I and Coffee Breakoster Session I and Coffee Breakoster Session I and Coffee Breakoster Session I and Coffee Break

11.00 – 12.0011.00 – 12.0011.00 – 12.0011.00 – 12.0011.00 – 12.00 YYYYYoung Investigator Poung Investigator Poung Investigator Poung Investigator Poung Investigator Presentations Session Iresentations Session Iresentations Session Iresentations Session Iresentations Session IChair: Chair: Chair: Chair: Chair: Gary Lewin

Jing HuJing HuJing HuJing HuJing HuNeuroscience, MDCA tether required for touch

Ulrich SchweizerUlrich SchweizerUlrich SchweizerUlrich SchweizerUlrich SchweizerNeurobiology of Selenium, CharitéGenetic dissection of selenprotein functions in neuronalfunction and survival

Christel BonnasChristel BonnasChristel BonnasChristel BonnasChristel BonnasExperimental Neurology, CharitéNeuroprotection by novel endogenous non-hematopoieticerythropoietin derivates

Seija LehnardtSeija LehnardtSeija LehnardtSeija LehnardtSeija LehnardtCecilie-Vogt-Clinic for Neurology, CharitéA vicious cycle involving release of HSP60 from injured cellsand activation of TLR4 mediates neurodegeneration in theCNS

Scientific ProgramScientific ProgramScientific ProgramScientific ProgramScientific Program

12.00 – 13.0012.00 – 13.0012.00 – 13.0012.00 – 13.0012.00 – 13.00 LunchLunchLunchLunchLunch

13.00 – 15.0013.00 – 15.0013.00 – 15.0013.00 – 15.0013.00 – 15.00 Outdoor activitiesOutdoor activitiesOutdoor activitiesOutdoor activitiesOutdoor activities

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15.00 – 16.0015.00 – 16.0015.00 – 16.0015.00 – 16.0015.00 – 16.00 Lecture IVLecture IVLecture IVLecture IVLecture IVChair:Chair:Chair:Chair:Chair: Uwe HeinemannThomas MisgeldThomas MisgeldThomas MisgeldThomas MisgeldThomas MisgeldInstitut für Neurowissenschaften, Technische UniversitätMünchenIn vivo imaging of axon remodeling

16.00 – 17.3016.00 – 17.3016.00 – 17.3016.00 – 17.3016.00 – 17.30 PPPPPoster Session II and Coffee Breakoster Session II and Coffee Breakoster Session II and Coffee Breakoster Session II and Coffee Breakoster Session II and Coffee Break

17.30 17.30 17.30 17.30 17.30 ––––– 18.30 18.30 18.30 18.30 18.30 Lecture VLecture VLecture VLecture VLecture VChair: Chair: Chair: Chair: Chair: Ulrich DirnaglBrian MacVicarBrian MacVicarBrian MacVicarBrian MacVicarBrian MacVicarDepartment of Psychiatry, Brain Research Center, UBCHospital, Vancouver, CanadaAstrocyte regulation of the cerebrovasculature

18.30 – 19.3018.30 – 19.3018.30 – 19.3018.30 – 19.3018.30 – 19.30 DinnerDinnerDinnerDinnerDinner

20.3020.3020.3020.3020.30 FFFFFarewell Parewell Parewell Parewell Parewell Party SFB 507 and Disco Nightarty SFB 507 and Disco Nightarty SFB 507 and Disco Nightarty SFB 507 and Disco Nightarty SFB 507 and Disco Night

Scientific ProgramScientific ProgramScientific ProgramScientific ProgramScientific Program

SaturdaySaturdaySaturdaySaturdaySaturday, June 7, 2008, June 7, 2008, June 7, 2008, June 7, 2008, June 7, 2008

8.00 – 9.008.00 – 9.008.00 – 9.008.00 – 9.008.00 – 9.00 BreakfastBreakfastBreakfastBreakfastBreakfast

99999.00 – 10.00.00 – 10.00.00 – 10.00.00 – 10.00.00 – 10.00 YYYYYoung Investigator Poung Investigator Poung Investigator Poung Investigator Poung Investigator Presentations Session IIresentations Session IIresentations Session IIresentations Session IIresentations Session IIChair: Chair: Chair: Chair: Chair: Dietmar Schmitz

Hannes SchmidtHannes SchmidtHannes SchmidtHannes SchmidtHannes SchmidtDevelopmental Neurobiology, MDCA cyclic GMP signaling pathway essential for sensory axonbifurcation

Oliver KannOliver KannOliver KannOliver KannOliver KannNeurophysiology, CharitéMitochondria and neuronal activity: insights from the healthyand the epileptic hippocampus

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Ana-Luisa PinaAna-Luisa PinaAna-Luisa PinaAna-Luisa PinaAna-Luisa PinaCenter for Regenerative Therapies, CharitéPigment epithelium derived factor during postnataldevelopment, ageing and disease of the Nervous System

Lars BertramLars BertramLars BertramLars BertramLars BertramGenetics and Aging Research Unit, MINDImplications from systematic meta-analyses of geneticassociation studies of Alzheimer’s disease and Parkinson’sdisease

10.00 – 11.0010.00 – 11.0010.00 – 11.0010.00 – 11.0010.00 – 11.00 PPPPPoster Session II and Coffee Breakoster Session II and Coffee Breakoster Session II and Coffee Breakoster Session II and Coffee Breakoster Session II and Coffee Break

11.00 – 11.4511.00 – 11.4511.00 – 11.4511.00 – 11.4511.00 – 11.45 YYYYYoung Investigator Poung Investigator Poung Investigator Poung Investigator Poung Investigator Presentations Session IIIresentations Session IIIresentations Session IIIresentations Session IIIresentations Session IIIChair:Chair:Chair:Chair:Chair: Christoph Stein (Berlin)

Hagen WHagen WHagen WHagen WHagen WendeendeendeendeendeMouse Genetics, MDCc-Maf is an important regulator of myelination in theperipheral nervous system

Nikolas OffenhauserNikolas OffenhauserNikolas OffenhauserNikolas OffenhauserNikolas OffenhauserExperimental Neurology, CharitéAlterarions in neurometabolic-neurovascular coupling bycortical spreading depression in rat somatosensory cortex

Sebastian IvensSebastian IvensSebastian IvensSebastian IvensSebastian IvensNeurophysiology, CharitéDifferential mechanisms underlying altered neuronalexcitability following blood-brain barrier disruption

11.45 - 12.4511.45 - 12.4511.45 - 12.4511.45 - 12.4511.45 - 12.45 Lecture VILecture VILecture VILecture VILecture VIChair:Chair:Chair:Chair:Chair: Frauke ZippBritta EngelhardtBritta EngelhardtBritta EngelhardtBritta EngelhardtBritta EngelhardtTheodor-Kocher-Institut, Universität Bern, SwitzerlandMolecular mechanisms involved in tissue specific leukocytediapedesis across the endothelium

12.45 - 13.0012.45 - 13.0012.45 - 13.0012.45 - 13.0012.45 - 13.00 PPPPPoster Poster Poster Poster Poster Prize Awardingrize Awardingrize Awardingrize Awardingrize Awarding

13.0013.0013.0013.0013.00 Lunch and DepartureLunch and DepartureLunch and DepartureLunch and DepartureLunch and Departure

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PPPPPoster Poster Poster Poster Poster Presentations - Session Iresentations - Session Iresentations - Session Iresentations - Session Iresentations - Session I

PPPPPostersession Iostersession Iostersession Iostersession Iostersession I

1. DETECTION OF SIGNALING PATHWAY ACTIVATION IN RAT DRG-NEURONS BY AUTOMATED RELATIVEIMMUNOFLUORESCENCEAndres, C.; Hucho, T.Max Planck Institute for Molecular Genetics, Department Ropers, Berlin

2. DEVELOPMENT OF GENETIC TOOLS FOR SELECTIVE AND REVERSIBLE SILENCING OF ION CHANNELSUSING NATURAL TOXINSAuer, S.; Jüttner, R.; Ibanez-Tallon, I.Max-Delbrück Center for Molecular Medicine, Department of Neurobiology, Berlin

3. A MODEL OF NEURONAL COLOR CODING AND COLOR SENSATIONS IN MANBackhaus, W.G.K.Technische Universität Berlin, Theoretische und Experimentelle Biologie, Neurowissenschaften, FR 2-1 R 2073,Berlin

4. SODIUM CURRENTS IN IMMORTALIZED AND DEVELOPING STRIATAL PROGENITOR CELLSBattefeld, A.; Wasner, U.; Geist, B.; Nitsch, R.; Strauss, U.Charité Universitätsmedizin Berlin, Centre for Anatomy, Institute for Cell and Neurobiology, Berlin

5. ALCOHOL MEDIATES ASSOCIATION BETWEEN STRIATAL REWARD PROCESSING AND IMPULSIVENESSBeck, A.; Deserno, L.; Kahnt, T.; Wrase, J.; Heinz, A.Charité - Universitätsmedizin Berlin, CCM, Department of Psychiatry and Psychotherapy, Berlin

6. ROLE OF EXTRACELLULAR SIGNAL-RELATED KINASE 1 IN THE REGULATION OF NEUROINFLAMMATIONBendix, I.; Pfueller, C.F.; Leuenberger, T.; Siffrin, V.; Schulze-Topphoff, U.; Zipp, F.; Waiczies, S.Charite University Medicine Berlin, Cecile Vogt Clinic for Neurology at the HKBB, Berlin

7. CLC-2 CL- CURRENTS IN OLIGODENDROCYTES FROM ACUTE SLICES IN THE MOUSE CORPUS CALLOSUMBenedetti, B.; Haas, B.; Jentsch, T. J., Kettenmann, H.MDC, Cellular Neuroscience, Berlin

8. SYNERGISTIC EFFECTS OF IL-4 AND IL-10 ON AXONAL OUTGROWTH AND REINNERVATIONBoato, F.; Hechler, D.; Rosenberger, K.; Nitsch, R.; Hendrix, S.Charité – Universitätsmedizin, Institute for Cell Biology and Neurobiology, Center for Anatomy, Berlin

9. MIGRATION OF GENE-MODIFIED BONE MARROW-DERIVED CELLS INTO MOUSE RETINASBoettcher, C.; Beck, S.; Bauer, R.; Seeliger, M.W.; Priller, J.Charité Campus Mitte, Laboratory of Molecular Psychiatry, Berlin

10. MECHANISMS AND FUNCTIONAL ROLE OF IMMUNE RESPONSE FOLLOWING AXONAL LESIONBrandt, C.; Meisel, C.; Richter, D.; Ellinghaus, A.; Bechmann, I.; Nitsch, R.Institute of Cellbiology and Neurobiology, Center for Anatomy, Berlin

11. B56BETA INTERACTS WITH CALEB/NGC AND INHIBITS CALEB/NGC-MEDIATED DENDRITIC BRANCHINGBrandt, N.; Nitsch, R.; Schumacher, S.Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Center for Anatomy, Berlin

12. LATERAL LINE RESPONSES INTEGRATE THE WAVE CURVATUREBranoner, F.; Ziehm, U.; Zhivkov, Z.; Schuldt, C.; Behrend, O.Humboldt Universität Berlin, Institute of Biology, Aquatic Bioacoustics Laboratory, Berlin

ThursdayThursdayThursdayThursdayThursday, June 5, 15.35 - 17.00, June 5, 15.35 - 17.00, June 5, 15.35 - 17.00, June 5, 15.35 - 17.00, June 5, 15.35 - 17.00FFFFFridayridayridayridayriday, June 6, 10.00 - 11.00, June 6, 10.00 - 11.00, June 6, 10.00 - 11.00, June 6, 10.00 - 11.00, June 6, 10.00 - 11.00

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13. DYSFERLIN DEFICIENT MUSCULAR DYSTROPHY FEATURES AMYLOIDOSISCarl, M.; Zabojszcza, J.; Bushby, K.; Moore, S.A.; Röcken, C.; Spuler, S.Experimental and Clinical Research Center (ECRC), Charité Universitary Medical S, Muscle Research Unit, Berlin

14. ROLE OF G-ALPHAI2 ON ZO-1 UNDER EPINEPHRINE STIMULATIONCastro Villela, V.; Sing Bal, M.; Piontek, J.; Rückert, C.;. Nürnberg, B.; Blasig, I.E.Leibniz-Institut für Molekulare Pharmakologie, Molecular Cell Physiology, Berlin

15. PERSONALITY TRAITS AND STRUCTURAL BRAIN ALTERATIONS IN HEALTHY SUBJECTS: A MORPHOMETRICANALYSIS OF MRI-DATACharlet, K.; Gudlowski, Y.; Kaufmann, C.; Schubert, F.; Heinz, A.; Gallinat, J.Charité - University Medicine Berlin, Department of Psychiatry and Psychotherapy Campus Mitte, Berlin

16. AMEBOID MICROGLIA IN DEVELOPING BRAIN INDIRECTLY RESPOND TO GABA- AND GLUTAMATERGICACTIVITIES BY SENSING THE RESULTING INCREASE IN EXTRACELLULAR POTASSIUMCheung, G.; Kann, O.; Färber, K.; Kettenmann, H.MDC, Cellular Neuroscience, Berlin

17. ROLE OF EXTRACELLULAR MATRX IN SENSORY MECHANOTRANSDUCTIONChiang, L.Y.; Hu, J.; Erdmann, B.; Koch, M.; Lewin, G.R.Max-Delbrück Centrum, Neuroscience, Berlin

18. MODULATION OF NEURONAL MEMBRANE PROPERTIES BY THE COXSACKIEVIRUS-ADENOVIRUS RECEPTORCholewa, J.; Jüttner, R.; Rathjen, F.G.Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Developmental Neurobiology, Berlin

19. PRG-5 IN CULTURED NEURONS INDUCTS DENDRITIC-SPINES FORMATIONCoiro, P.; Velmans, T.; Bräuer, A.U.Charite, Institut für Zell- und Neurobiologie, Berlin

20. DEVELOPMENTALLY REGULATED EXPRESSION, LOCALIZATION AND FUNCTIONAL REGULATION OFCALEB, AN EGF-LIKE PROTEINCraveiro, R.B.; Jüttner, R.; Rathjen, F.G.Max-Delbrück-Centrum für Molekulare Medizin, Neurobiology, Berlin

21. COMPLEMENTARY CONTRIBUTIONS OF PREFRONTAL NEURON CLASSES IN ABSTRACT NUMERICALCATEGORIZATIONDiester, I.Hertie Institute for Clinical Brain Research, Cognitive Neurology, Tübingen

22. ALPHA-1A ADRENERGIC RECEPTORS REGULATE NEUROGENESIS AND COGNITIVE FUNCTIONDoze, V.; Boese, S.; Knudson, C.; Goldenstein, B.; Schlosser, D.; Carr, P.; Perez, D.Univ. of North Dakota School of Medicine Health Sciences, Pharmacology, Physiology Therapeutics, GrandForks, North Dakota

23. ‘NORMAL’ AND ‘INVERSE’ NEUROVASCULAR COUPLING AND SUPPRESSION OF LOW-FREQUENCYVASCULAR FLUCTUATIONS DURING CORTICAL SPREADING DEPOLARISATION IN THE HUMAN BRAINDreier, J.P.; Major, S.; Manning, A.; Woitzik J.; Drenckhahn, C.; Steinbrink, J.; Tolias C.; Einhäupl, K.M.; Fabricius,M.; Hartings, J.A.; Vajkoczy, P.; Lauritzen, M.; Dirnagl U.; Bohner, G.; Strong,Charité University Medicine Berlin, Neurology, Berlin

24. GLYCINERGIC TONIC INHIBITION OF HIPPOCAMPAL NEURONS WITH DEPOLARISING GABAERGICTRANSMISSION ELICITS HISTOPATHOLOGICAL SIGNS OF TEMPORAL LOBE EPILEPSYEichler, S.A.; Kirischuk, S.; Jüttner, R.; Schäfermeier, P.K.; Legendre, P; Lehmann, T.N.; Gloveli, T.; Grantyn, R.;Meier, J.C.MDC, Neuroscience, Berlin

List of PList of PList of PList of PList of Poster Poster Poster Poster Poster Presentationsresentationsresentationsresentationsresentations P P P P Postersession Iostersession Iostersession Iostersession Iostersession I

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25. COMPLEMENT C1Q IS A PROINFLAMMATORY STIMULUS, AND MANNOSE-BINDING LECTIN IS AN ANTI-INFLAMMATORY STIMULUS, FOR MICROGLIAL ACTIVATIONFärber, K.; Cheung, G.; Mitchell, D.; Wallis, R.; Kettenmann, H.MDC, Cellular Neuroscience, Berlin

26. PROTEASOME ACTIVITY RESTRICTS LONG-TERM MEMORY FORMATION IN HONEYBEES (APIS MELLIFERA)Felsenberg, J.; Eisenhardt, D.Freie Universität Berlin, Neurobiologie, Berlin

27. CORTICAL CAPILLARIES POSSESS ACTIVE CONTRACTILE ABILITIES IN SLICE AND IN VIVO: A TWO-PHOTONSTUDYFernández-Klett, F.; Offenhauser, N.; Dirnagl, U.; Priller, J.; Lindauer, U.Charité - Universitätsmedizin Berlin, Department of Experimental Neurology, Berlin

28. HETEROSYNAPTIC PLASTICITY AT THE HIPPOCAMPAL OUTPUTFidzinski, P.; Heinemann, U.; Behr, J.Charité Universitaetsmedizin, Institute for Neurophysiology, Berlin

29. INVESTIGATION OF SIGNALLING PATHWAYS NECESSARY FOR CALEB/NGC- DRIVEN DENDRITIC SPINECOMPLEXITYFranke, K.; Brandt, N.; Nitsch, R.; Schumacher, S.Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin; Centre for Anatomy, Berlin

30. NEUROVASCULAR COUPLING AND CEREBRAL METABOLIC RATE OF OXYGEN: EFFECTS OF BRAINHYPOTHERMIAFüchtemeier, M.; Offenhauser N.; Leithner C.; Steinbrink J.; Kohl-Bareis M.; Dirnagl U.; Lindauer U.; Royl G.Charite Universitätsmedizin Berlin, Department of Experimental Neurology, Berlin

31. ROLE OF THE TSH1 GENE IN OLFACTORY BULB - DEVELOPMENTGarratt, A.N.; Birchmeier, C.; Rocca, E.Max-Delbrueck-Center for Molecular Medicine, Department of Neurosciences, Berlin

32. EXPRESSION ANALYSIS OF THE PLASTICITY RELATED GENE-1Geist, B.; Trimbuch, T.; Ninnemann, O.; Nitsch, R.Charité-Universitätsmedizin Berlin, Center für Anatomie, Institut für Zell- und Neurobiologie, Berlin

33. MACROPHAGE/MICROGLIA ACTIVATION AND ENGRAFTMENT DURING PERSISTENT BORRELIAL CNSINFECTIONGelderblom, H.; Londono, D.; Boettcher, C.; Cadavid, D.; Priller, J.Charite-Klinik f. Psychiatrie u. Psychotherapie, Charite Campus Mitte, Molekulare Psychiatrie, Berlin

34. COGNITIVE CONTROL OF GOAL-DIRECTED BEHAVIOR: EVENT-RELATED POTENTIALS ASSOCIATED WITHSELF-GENERATED AND EXTERNALLY INDUCED FAILUREGentsch, A.; Ullsperger, P.; Kathmann, N.; Endrass, T.; Ullsperger, M.Berlin School of Mind and Brain, Berlin

35. APOLIPOPROTEIN E DEFICIENCY ENHANCES TAU HYPERPHOSPHORYLATION IN P301L MUTANT HUMANTAU MICEGlöckner, F.; Meske, V.Charité-Universitätsmedizin Berlin, Zentrum für Anatomie, Berlin

36. TRPV1, A SYNAPTIC PROTEINGoswami, C.; Hucho, T.Max Planck Institute for Molecular Genetics, Signal Transduction in Pain and Mental Retardation, Berlin

37. EFFECTS OF SALICYLATE APPLICATION ON THE SPONTANEOUS ACTIVITY IN BRAIN SLICES OF THEMOUSE COCHLEAR NUCLEUS, MEDIAL GENICULATE BODY AND PRIMARY AUDITORY CORTEXGötze, R.; Basta, D.; Ernst, A.Humboldt-University Berlin, Department of Biology, Neurootological Team, Berlin

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38. ACUTE AND LONG-TERM EFFECTS OF NOISE EXPOSURE ON THE ASCENDING AUDITORY PATHWAYEVALUATED WITH MANGANESE-ENHANCED MAGNETIC RESONANCE IMAGING (MEMRI)Gröschel, M.; Müller, S.; Götze, R.; Bauknecht, C.; Klingebiel, R.; Ernst, A.; Basta, D.Humboldt-University of Berlin, Institute of Biology, Berlin

39. ALTERATIONS IN THE ENTORHINAL CORTEX NETWORK OSCILLATIONS IN A MOUSE MODEL OF MESIALTEMPORAL LOBE EPILEPSYGurgenidze, S.; Dugladze, T.; Heinemann, U.; Gloveli, T.Institute for Neurophysiology, Charite Universitätsmedizin Berlin

40. FREQUENCY AND PHENOTYPE OF NK CELLS IN MULTIPLE SCLEROSISHamann, I.; Paterka, M.; Prozorovski, T.; Pitarokoili, K.; Zipp, F.; Infante-Duarte, C.Charité - University Medicine Berlin, Cecilie Vogt Clinic of Neurology, Berlin

41. DENSITY OF ENKEPHALIN EXPRESSING STRIATAL PROJECTION NEURONS AND ENTOPEDUNCULARDYNORPHIN IMMUNOREACTIVITY ARE UNALTERED IN A MODEL OF PAROXYSMAL DYSTONIAHamann, M.; Kreil, A.; Richter, A.Institute of Pharmacology and Toxicology, Freie Universität Berlin, Dept. of Veterinary Medicine, Berlin

42. GAMMA OSCILLATIONS AND SPONTANEOUS NETWORK ACTIVITY IN THE HIPPOCAMPUS ARE HIGHLYSENSITIVE TO DECREASES IN PO2 AND CONCOMITANT CHANGES IN MITOCHONDRIAL REDOX STATEHuchzermeyer, C.; Albus, K.; Gabriel, H.J.; Otáhal, J.; Taubenberger, N.; Heinemann, U.; Kovács, R.; Kann, O.Charité, Institut für Neurophysiologie, Berlin

43. MOLECULAR INTERACTIONS BETWEEN STOMATIN-LIKE PROTEINS AND ACID-SENSING ION CHANNELSJira, J.; Heppenstall, P.Charité CBF, Klinik fuer Anaesthesiologie, Berlin

44. CALEB, AN ACTIVITY-REGULATED PROTEIN, IS INVOLVED IN THE ESTABISHMENT OF SYNAPTICCONNECTIONS IN THE CEREBELLUMJüttner, R.; Craveiro, R.B.; Montag, D.; Rathjen, F.G.Developmental Neurobiology, MDC, Berlin

45. EARLY MATURATION OF GABAERGIC SYNAPSES IN MOUSE RETINAL GANGLION CELLSJüttner, R.; Unsoeld, T.; Stradomska, A.M.; Wang, R.; Rathjen, F.G.Theodor-Kocher-Institut, Universität Bern

46. LYSOPHOSPHATIDIC ACID IN SYNAPSOGENESISKieselmann, O.; Grantyn, R.; Singh, B.; Aoki, J.; Nitsch, R.; Bräuer, A.U.Charité, Centrum for Anatomy, Cell- and Neurobiology, Berlin

47. DRUG TRANSPORTERS IN HUMAN EPILEPTIC BRAIN – FUNCTIONAL STUDIESKim, S.; Sandow, N.; Kovacs, R.; Raue, C.; Päsler, D.; Fidzinski, P.; Alam, A.; Klaft, Z.J.; Leite Antonio, L.;Heinemann, U.; Gabriel, S.; Lehmann, T.N.Charité, Institut für Neurophysiologie, Berlin

48. DEVELOPMENTAL DOWN-REGULATION OF EXCITATORY GABAERGIC TRANSMISSION IN NEOCORTICALLAYER I VIA PRESYNAPTIC ADENOSINE A1 RECEPTORSKirischuk, S.; Grantyn, R.; Dvorzhak, A.; Kirmse, K.Institut für Neurophysiolgie, Charité-Universität-Medizin Berlin, Developmental Physiology, Berlin

49. ACTIVITY OF THE GABA TRANSPORTER 1 REGULATES GABAERGIC SYNAPTIC TRANSMISSION IN STRIATALPROJECTION NEURONSKirmse, K.; Grantyn, R.Inst. for Neurophysiology - Charité, Developmental Physiology, Berlin

50. METABOLIC CONSEQUENCES OF STORE OPERATED CAPACITATIVE CA2+ ENTRYKovács, R.; Taubenberger, N.R.; Huchzermeyer, C.; Heinemann, U.; Kann, O.Charite-Universitaetsmedizin, Berlin, Inst. for Neurophysiology, Berlin

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51. ESTROGEN INDUCES TRPV1-DEPENDENT CYTOSKELETAL REARRANGEMENTKuhn, J.; Goswami, C.; Hucho, T.MPI for Molecular Genetics, Berlin

52. SEQUENTIAL MATURATION OF SENSORY NEURON MECHANOTRANSDUCTION DURING EMBRYONICDEVELOPMENTLechner, St.G.; Wang, R.; Frenzel, H.; Lewin, G.R.Max Delbrück Centrum für Molekulare Medizin (MDC) Berlin-Buch, Neurowisssenschaften, Berlin

53. DOES AGING INFLUENCE PHYSIOLOGICAL NEUROVASCULAR COUPLING? A COMBINED DC-MAGNETOENCEPHALOGRAPHIC AND TIME-RESOLVED NEAR-INFRARED SPECTROSCOPIC STUDYLeistner, S.; Sander, T.H.; Wabnitz, H.; Burghoff, M.; Curio, G.; Macdonald, R.; Trahms, L.J; Mackert, B.M.Charité, Campus Benjamin Franklin, Department of Neurology, Berlin

54. MOLECULAR MECHANISMS UNDERLYING AMYLOID BETA MODULATING EFFECTS OF FENOFIBRATEAND CELEBREXLill, C.M.; Thomas, A.V.; Herl, L.; Deng, A.; Hyman, B.T.; Berezovska, O.Cecilie Vogt Clinic for Neurology, Charité Berlin, Neurology, Berlin

55. OLIGODENDROCYTIC COUPLING IN THE CNS WHITE MATTER RELATED TO CX47 EXPRESSIONMaglione, M.; Tress, O.; Willecke, K.; Kettenmann, H.MDC, Cellular Neuroscience, Berlin

56. DURATION OF CORTICAL SPREADING ISCHEMIA DEPENDS ON INTRACELLULAR CA2+-STORES.Major, S.; Dreier, J.P.Charité -Universitätsmedizin Berlin, Experimental Neurology, Berlin

57. CHARACTERIZATION OF THE PERIPHERAL OSMORECEPTORMarkworth, S.; Frahm, S.; IIbanez-Tallon, I.; Jordan, J.; Lewin, G.R.MDC, Neuroscience, Berlin

58. THE POTASSIUM THRESHOLD FOR CORTICAL SPREADING DEPRESSION IS INFLUENCED BY AGE ANDEPILEPTIC CHANGES IN RAT AND HUMAN NEOCORTEXMaslarova, A.; Alam, M.; Dreier, J.P.Charité, Berlin, Experimental Neurology, Berlin

59. GABAB RECEPTOR MEDIATED INHIBITION IN MESIAL TEMPORAL LOBE EPILEPSYMaziashvili, N.; Dugladze, T.; Heinemann, U.; Gloveli, T.Institute for Neurophysiology, Charité-Universitätsmedizin, Berlin

FFFFFridayridayridayridayriday, June 6, , June 6, , June 6, , June 6, , June 6, 16.00 - 17.3016.00 - 17.3016.00 - 17.3016.00 - 17.3016.00 - 17.30SaturdaySaturdaySaturdaySaturdaySaturday, June 7, 10.00 - 11.00, June 7, 10.00 - 11.00, June 7, 10.00 - 11.00, June 7, 10.00 - 11.00, June 7, 10.00 - 11.00

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60. HEXOKINASE II - A GLUCOSE DEPENDENT MEDIATOR OF SURVIVALMergenthaler, P.; Freyer, D.; Neeb, L.; Megow, D., Harms, C.; Priller, J.; Dirnagl, U.; Meisel, A.Charité Universitätsmedizin Berlin, Experimentelle Neurologie, Berlin

61. ROLE OF DIFFERENT CTL-EFFECTOR MOLECULES IN DAMAGING THE NEURO-AXONAL UNIT IN VIVOMerkler, D.; Bergthaler, A.; Schedensack, M.; Horvath, E.; Kerschensteiner, M.; Misgeld, T.; Brück, W.; Pinschewer,D.Georg-August-University, Neuropathology, Göttingen

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62. MODULATION OF THERMAL NOCICEPTION BY NGF AND SCF/C-KIT SIGNALINGMilenkovic, N.; Frahm, C.; Griffel, C.; Erdmann, B.; Birchmeier, C.; Garratt, A.; Lewin, G.R.Max-Delbrück Centrum für molekulare Medizin, Berlin

63. ANALYSIS OF OPIOID RECEPTOR/K+ CHANNEL COUPLING IN SENSORY NEURONSNockemann, D.; Stein, C.; Heppenstall, P.A.Klinik für Anästhesiologie und operative Intensivmedizin, Charité, Berlin

64. DOES ENOTHELIN-1 INDUCE CORTICAL SPREADING DEPOLARIZATION (CSD) VIA A DIRECT EFFECT ONTHE VASCULATURE?Oliveira-Ferreira, A.I.; Alam, M.; Major, S.; Dreier, J.P.Charité University Medicine, Experimental Neurology, Berlin

65. RHOG IS A TARGET FOR MI-RNA DEPENDENT REGULATION OF EXPRESSION AND HAS AN IMPACT ONAXONAL BRANCHINGOtto, W.; Baumgart, J.; Dulinski, M.; Wulczyn, F.G.; Nitsch, R.; Schumacher, S.Institute of Cell Biology and Neurobiology, Charité, Center for Anatomy, Berlin

66. THE FUNCTION OF THE COXSACKIEVIRUS-ADENOVIRUS RECEPTOR (CAR) IN THE DEVELOPING NERVOUSSYSTEM – ITS SELF-ASSOCIATION AND INTERACTION WITH ECM GLYCOPROTEINSPatzke, C.; Dorner, A.; Behlke, J.; Müller, E.C.; Otto, A.; Schmidt, H.; Kröger, S.; Rathjen, F.G.MDC, Neuronal Connectivity, AG Rathjen, Berlin

67. CORTICAL GLUTAMATE IS LINKED TO REWARD RELATED VENTRAL STRIATE ACTIVITY – A COMBINED FMRIAND 1H-MRS STUDYC. Pehrs, J. Reuter, N. Klein, M. Voss, , T. Dembler, Y. GudlowskiCharité Campus Mitte, Berlin

68. COMBINED ANTIDEMENTIVE TREATMENT IMPROVES COGNITIVE ABILITIES ONLY IN MCI-ADPeters, O.; Lorenz, D.; Möller, H-J.; Frölich, L.; Heuser, I.Charité - University Medicine Berlin, Department of Psychiatry and Psychotherapy, CBF, Berlin

69. NKCC1-DEPENDENT GABAERGIC EXCITATAION DRIVES SYNAPTIC NETWORK MATURATION DURING EARLYHIPPOCAMPAL DEVELOPMENTPfeffer, C.; Stein, V.; Keating, D.; Maier, H.; Rudhard, Y.; Hentschke, M.; Rune, G.; Jentsch, T.J.; Hübner, C.A.Max-Delbrück-Centrum for Molecular Medicine, Physiology and Pathology of Ion Transport, Berlin

70. FUNCTIONAL EFFECT OF A MUTANT OF THE SECOND EXTRACELLULAR LOOP OF CLAUDIN-5 IN THEBLOOD-BRAIN BARRIERPiehl, C.; Piontek, J.; Winkler, L.; Blasig, I. E.Leibniz-Institut für Molekulare Pharmakologie, Berlin

71. TOOLS FOR THE GENERATION OF SPECIFIC DRG CELL STRUCTURES IN VITROPoole, K.; Hu, J.; Lewin, G.Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Function and Dysfunction of the NervousSystem, Berlin

72. SIRT1 CRITICALLY CONTRIBUTES TO THE REDOX-DEPENDENT FATE OF NEURAL PROGENITORSProzorovski, T.; Schulze-Topphoff, U.; Glumm, R.; Baumgart, J.; Schröter, F.; Ninnemann, O.; Siegert, E.; Bendix,I.; Nitsch, R.; Brüstle, O.; Zipp, F.; Aktas O.Charite Universitätsmedizin Berlin und MDC Berlin, Cecilie-Vogt-Klinik für Neurologie, Berlin

73. CIRCADIAN RHYTHM IN PHONETIC SPEECH PERCEPTIONPusch, K.; Rosenberg, J., Sommer, W.; Ronneberg, T.; Dietrich, R.Humboldt University of Berlin, German Language and Linguistics, Berlin

74. DIFFERENCES IN REWARD PROCESSING ACROSS THE LIFESPANRapp, M.A.; Wrase, J.; Schlagenhauf, F.; Beck, A.; Schulte, S.; Gallinat, J.; Heinz, A.Charité Campus Mitte, Psychiatric University Clinic at St. Hedwig’s Hospital, Geriatric Psychiatry Center, Berlin

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75. ASTROCYTES RESPOND TO THE CALYX OF HELD ACTIVITYReyes-Haro, D.; Mueller, J.; Pivneva, T.; Nolte, C.; Luebcke, J.; Kettenmann, H.Max Delbrueck Center, Neurosciences, Berlin

76. KV7 (KCNQ) POTASSIUM CHANNEL OPENERS ATTENUATE LEVODOPA-INDUCED DYSKINESIAS IN 6-OHDA-LESIONED RATSRichter, A.; Sander, S.E.Faculty of Veterinary Medicine, FU Berlin, Department of Pharmacology and Toxicology, Berlin

77. INTERLEUKIN-1BETA AND NEUROTROPHIN-3 APPLICATION FOR THE TREATMENT OF SPINAL CORDINJURYRosenberger, K.; Hechler, D.; Skreka, K.; Nitsch, R.; Hendrix, S.Charité-Universitätsmedizin Berlin, Institute for Cell Biology and Neurobiology, Center for Anatomy, Berlin

78. A SELF-MADE MEDIUM SUPPLEMENT FOR PRIMARY NEURONAL CULTURE REVEALS THE ROLE OFSELENIUM FOR NEURONAL SURVIVALRoth, S.; Wirth, E.K.; Schweizer, U.Charité Universitätsmedizin - Berlin, Neurowissenschaftliches Forschungszentrum, Berlin

79. COMBINATION OF DC-MAGNETOENCEPHALOGRAPHY AND TIME-RESOLVED NEAR-INFRAREDSPECTROSCOPY FOR THE STUDY OF NEURO-VASCULAR COUPLINGSander, T.H.; Leistner, S.; Wabnitz, H.; Burghoff, M.; Curio, G.; Mackert, B.M.; Macdonald, R.;Trahms, L.Physikalisch-Technische BA, AG 8.21, Berlin

80. DRUG RESISTANCE IN THE HUMAN EPILEPTIC HIPPOCAMPUS AND TEMPORAL CORTEXSandow, N.; Kim, S.; Raue, C.; Paesler, D.; Antonio, L.L; Kovacs, R.; Fidzinski, P.; Alam, M.; Klaft, Z.J.;Heinemann, U.; Gabriel, S.; Lehmann, T.N.Charité, J. Mueller Institut fuer Physiologie, Berlin

81. TOLL-LIKE RECEPTOR 4/MYD88 PATHWAY MEDIATES THE MICROGLIAL PROINFLAMMATORY RESPONSETO THROMBIN-ASSOCIATED PROTEIN COMPLEXESScheffel, J.; van Rossum, D.; Weinstein, J.R.; Dihazi, H.; Regen, T.; Brück, W.; Kettenmann, H.; Prinz, M.; Möller,T.; Hanisch, U.K.University of Göttingen, Institute of Neuropathology, Göttingen

82. NONVIRAL TRANSFECTION ENABLES STABLE GENE TRANSFER INTO MURINE MESENCHYMAL STEMCELLS DERIVED FROM BONE MARROWScheibe, F.; Priller, J.Charité - University Medicine Berlin, Laboratory for Molecular Psychiatry/ Experimental Neurology, Berlin

83. ASTROCYTES IN SITU RESPOND TO THE ANTI-DEPRESSANT CITALOPRAM INDEPENDENT FROM NEURONALACTIVITYSchipke, C.G.; Heuser, I.; Peters, O.Charité, Department of Psychiatry and Psychotherapy, CBF, Berlin

84. EVALUATION OF THE RAT FREE EXPLORATORY BEHAVIOUR AS AN ANIMAL TEST FOR TRAIT ANXIETY INRATSSchmidt, N.; Voigt, J.P.; Bert, B.; Fink, H.; Rex, A.Freie Universität Berlin, Institute of Pharmacology and Toxicology, Berlin

85. STIMULUS DEPENDING CHANGES OF EXTRACELLULAR GLUCOSE IN THE RAT HIPPOCAMPUS DETERMINEDBY IN VIVO MICRODIALYSISRex, A., Bert, B., Fink, H., Voigt, J. P.Freie Universität Berlin, Institute of Pharmacology and Toxicology, Berlin

86. METABOLIC CONSEQUENCES OF CAVEOLIN 3 MUTATIONSSchmidt, S.; Mähler, A.; Boschmann, M.; Hermsdorf, M.; Weber, M.A .; Spuler, S.ECRC, Charite, Myology, Berlin

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87. EFFECTS OF UNCERTAINTY ON PERFORMANCE MONITORING IN OLDER ADULTSSchreiber, M.; Kathmann, N.; Endrass, T.Departement of Psychology, Humboldt University, Berlin

88. NOW YOU’LL FEEL IT – NOW YOU WON’T: - PRE-STIMULUS EEG CORRELATES OF CONSCIOUSPERCEPTIONSchubert, R.; Haufe, S.; Blankenburg, F.; Villringer, A.; Curio, G.Charité, Universitätsmedizin Berlin, Campus Benjamin Franklin, AG Neurophysik, Klinik für Neurologie undklinische Neurophysiologie, Berlin

89. PERFORMANCE MONITORING AND DECISION MAKING IN PATIENTS WITH BORDERLINE PERSONALITYDISORDERSchuermann, B.; Kathmann, N.; Renneberg, B.; Endrass, T.Humboldt-University of Berlin, Clinical Psychology, Berlin

90. EXPRESSION OF A CALCIUM SENSOR PROTEIN IN MICROGLIASeifert, S.; Färber, K.; Uckert, W.; Kettenmann, H.MDC Berlin, Cellular Neuroscience, Berlin

91. IN VIVO IMAGING OF LYMPHOCYTES IN THE CNS REVEALS DYNAMIC T CELL COMPARTMENTALIZATIONSiffrin, V.; Brandt, A.U.; Radbruch, H.; Herz, J.; Boldakowa, N.; Leuenberger, T.; Werr, J.; Schulze-Topphoff, U.;Nitsch, R.; Zipp, F.Charité - Universitätsmedizin Berlin und MDC Berlin, Cecilie-Vogt-Klinik für Neurologie, Berlin

92. A MOLECULAR DISSECTION OF TRPV1 SENSITISATION USING THE NAKED MOLE-RATSmith, E.St.J.; Anirudhan, G.; Lewin, G.R.Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Neuroscience, Berlin

93. PLASTICITY-RELATED GENE-1 SIGNAL TRANSDUCTIONSoriguera, A.; Kieselmann, O.; Singh, B.; Grantyn, R.; Swiercz, J.; Offermanns, S,; Nitsch, R.; Bräuer, A.U.Charité, Institute for Cell Biology and Neurobiology, Centrum for Anatomy, Berlin

94. ANALYSES OF PRG-1/RAS GRF-2 INTERACTION AND SIGNALING EFFECTSSoriguera, A.; Swiercz, J.M.; Offermanns, S.; Nitsch, R.; Bräuer, A.U.Charité, Center for Cell Biology and Neurobiology, PRG Research Group, Berlin

95. OPIOID WITHDRAWAL INCREASES TRPV1 ACTIVITY IN A PKA DEPENDENT MANNERSpahn, V.; Zöllner, C.Charité, CBF, Klinik für Anästhesiologie und operative Intensivmedizin, Berlin

96. INTERFERON-BETA REVERSIBLY ATTENUATES IH IN ADULT NEOCORTICAL PYRAMIDAL NEURONS INVITROStadler, K.; Bierwirth, C.; Strauss, U.Charité Universitätsmedizin Berlin, Center for Anatomy, Institute of Cell Biology and Neurobiology, Berlin

97. THE CONSOLIDATION OF AN EXTINCTION MEMORY DEPENDS ON THE MAGNITUDE OF THEPREDICTION ERROR DURING MEMORY RETRIEVALStollhoff, N.; Eisenhardt, D.*Freie Universität Berlin, Neurobiologie, Berlin

98. ANALYSIS OF PHOSPHORYLATION TARGETS OF THE CGKI IN DEVELOPING DORSAL ROOT GANGLIAWHICH ARE IMPORTANT FOR AXON BIFURCATION IN THE SPINAL CORDStonkute, A.; Schmidt, H.; Rathjen, F.G.Max-Delbrueck-Center for Molecular Medicine, Developmental Neurobiology, Berlin

99. PERINATAL HYPERPOLARIZATION-ACTIVATED CHANNEL SUBTYPE REARRANGEMENT IN NEOCORTICALPYRAMIDAL NEURONSStrauss, U.; Rocha, N.; Bräuer, A.U.Charite Universitätsmedizin Berlin, Institute for Cell and Neurobiology, Berlin

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100. PAIN ATTENUATION IN TETHERED-TOXIN TRANSGENIC MICE DUE TO REDUCED EXCITABILITY OF SENSORYNEURONSStürzebecher, A.; Hu, J.; Lewin, G.R.; Ibañez-Tallon, I.Max-Delbrück Centrum, Molecular Neurobiology, Berlin

101. ROLE OF PRG-1 IN HIPPOCAMPAL EXCITABILITYTrimbuch, T.; Beed, P.; Vogt, J.; Ninnemann, O.; Schuchmann, S.; Schuelke, M.; Baumgart, J.; Streu, N.; Geist,B.; Schlueter, L.; Meier, N.; Brunk, I.; Ahnert-Hilger, G.; Birchmeier, C.; Sendtner, M.; Braeuer, A.; Schmitz, D.;Nitsch, R.Charite, Institute of Cell- and Neurobiology, Berlin

102. THE INVOLVEMENT OF LIPID PHOSPHATE PHOSPHATASES IN CORTICOGENESISVelmans, T.; Gutsch, R.; Baumgart, J.; Nitsch, R.; Bräuer, AU.Charité – Universitätsmedizin, Institute for Cell Biology and Neurobiology, Berlin

103. LOWER MOTOR NEURON LOSS: MULTIPLE SCLEROSIS AS - A NEURODEGENERATIVE DISEASE?Vogt, J.; Paul, F.; Aktas, O.; Müller-Wielsch, K.; Dörr, J.; Bharathi, B.S.1*,; Dörr, S.; Schmitz, C.; Raine, C.S.;Tsokos, M.; Nitsch, R.; Zipp, F.Center for Anatomy, Institute of Cell Biology and Neurobiology, Berlin

104. ACUTE ALBUMIN EXPOSURE EFFECTS ARE STIMULATION FREQUENCY DEPENDENT AND SUGGESTPOTASSIUM BUFFERING IMPAIRMENTVoitcu, R.N.; Ivens, S.; Friedman, A.; Heinemann, U.Charité - Universitätsmedizin Berlin

105. THE ROLE OF THE THYROID HORMONE-SPECIFIC TRANSPORTER MCT8 IN CNS DEVELOPMENTWirth, E.K.; Roth, S.; Kinne, A.; Ambrugger, P.; Biebermann, H.; Grüters-Kieslich, A.; Schweizer, U.Charité, Institute for Experimental Endocrinology and Neuroscience Research Center, Berlin

106. RGS PROTEIN SUPPRESSION OF G ALPHA(O) PROTEIN-MEDIATED ALPHA-2A ADRENERGIC INHIBITIONOF MOUSE HIPPOCAMPAL CA3 EPILEPTIFORM ACTIVITYXu, K.; Goldenstein, B.; Nelson, B.; Luger, E.; Pribula, J., Wald, J.; Weinshenker, D.; Charbeneau, R.; Huang, X.;Neubig, T.; Doze, V.Univ. of North Dakota School of Medicine & Health Sciences, Pharmacology, Physiology & Therapeutics,Grand Forks, North Dakota, USA

107. PERIPHERAL AND CENTRAL ORGANIZATION OF THE LATERAL LINE PATHWAY IN XENOPUS LAEVISZhivkov, Z.; Schuldt, C.; Branoner, F.; Behrend, O.Humboldt Universität Berlin, Institute for Biology, Aquatic Bioacoustics Laboratory, Berlin

108. HYPERPHOSPHORYLATION OF TAU IN NPC-/- P301L-TAU+/+ MICEZonnur, S.; Goetz, J.; Ohm, T.G.Charité, Center for Anatomy, Berlin

109. ROLE OF THE FOXP2 GENE IN PROLIFERATION AND NEUROGENESIS IN THE VENTRICULAR ZONE OFZEBRA FINCHES, AN AREA DELIVERING NEWLY BORN NEURONS TO THE SONG NUCLEI AREA XSteffen SchulzFreie Universität Berlin, Institute of Biology, Department of Animal Behavior, Takustr. 6, D-15195 Berlin

110. FOXP2 TARGET GENES IN AREA X OF ZEBRA FINCHESIris AdamFreie Universität Berlin, Institute of Biology, Department of Animal Behavior, Takustr. 6, D-15195 Berlin

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MOLECULAR MECHANISMS INVOLVEDIN TISSUE SPECIFIC LEUKOCYTE DIA-PEDESIS ACROSS THE ENDOTHELIUMB. EngelhardtTheodor Kocher Institute, University of Bern, Bern,Switzerland

In multiple sclerosis and in its animal modelexperimental autoimmune encephalomyelitis (EAE),inflammatory cells migrate across the highlyspecialized endothelial blood-brain barrier (BBB) andgain access to the central nervous system (CNS). It iswell established that leukocyte recruitment acrossthis vascular bed is unique due to the predominantinvolvement of α4-integrins in mediating the initialcontact to as well as firm adhesion with theendothelium. In contrast, the involvement of theselectins, L-selectin, E- and P-selectin and theirrespective carbohydrate ligands such as PSGL-1 inthis process has been controversially discussed.Intravital microscopic analysis of immune cellinteraction with the BBB demonstrate a role for E-and P-selectin and their common ligand PSGL-1 inlymphocyte rolling in superficial brain microvessels.However, E- and P-selectin deficient SJL- or C57Bl/6 mice or PSGL-1-deficient C57Bl/6 mice developEAE indistinguishable from wild-type mice. Finally,although LFA-1/ICAM-1 interaction is involved in thediapedesis of leukocytes across the BBB the precisecellular pathway – transcellular or paracellular – andthe respective molecluar mechanisms involved inthis last step of leukocyte migration across the BBBremain to be investigated. The presentation willsummarized this current knowledge in the context ofa novel drug targeting α4-integrin for the treatmentof relapsing-remitting multiple sclerosis targeting thisprocess.

TOUCH, VISION AND MENTAL BODYREPRESENTATIONPatrick HaggardUniversity College London, Institute of CognitiveNeuroscience & Dept. Psychology, Alexandra House, 17Queen Square, London WC1N 3AR, U. K.

We experience our body in two quite distinct ways: as‘me’ via the somatosensory systems, and as avolumetric physical object, through the visual system.This talk investigates how the brain might link visualand somatosensory information to generate a singlecoherent sense of one’s body, of the stimulicontacting the body, and indeed of the bodily self.First, I will discuss top-down effects of visual bodyrepresentation on touch. Merely viewing the bodycan enhance the sense of touch. Evidence from

Abstracts of LecturesAbstracts of LecturesAbstracts of LecturesAbstracts of LecturesAbstracts of Lectures

OPTOGENETICS: DEVELOPMENT ANDNEUROPSYCHIATRY APPLICATIONASUBSET OF NATURALLY-OCCURRINGCarl DeisserothDepartment of Bioengineering, Department of Psychiatry,Stanford, USA

A subset of naturally-occurring microbial opsin genesencode light-sensitive transmembrane ionconductance regulators (all originally characterizedin non-neural systems, e.g. Hegemann et al., 1985;Kalaidzidis et al., 1998; Nagel et al., 2003; Zhanget al., 2008). If successfully adapted as aneuroscience technology, these proteins could beenormously significant, since controlling themembrane potential of targeted cell types with hightemporal resolution may allow elucidation of cellularcodes underlying neural circuit computation andbehavior. We have now introduced to neurobiologythree functionally distinct classes of these microbialopsin genes (VChR1, NpHR, and ChR2), allowingexcitation with yellow light, inhibition with yellow light,and excitation with blue light, respectively. Amongother crucial properties, we have found that all threeoperate on the millisecond timescale and can functionin mammalian neurons without addition of exogenouschemical cofactors, since the chromophore for theseproteins, all-trans retinal, appears to be already presentat sufficient levels in mammalian brains; moreoverwe have addressed light and gene delivery challenges,as integrated genetic, fiberoptic, and solid-state opticalapproaches have provided complementarytechnology to allow specific cell types, deep withinthe brain, to be controlled in freely behavingmammals. However, technical challenges still remain,including refining tolerability, optical properties, andcell type-specific targeting. We report here on 1)molecular engineering and membrane traffickingmanipulations to improve high-level expression ofthe opsin genes (leading to a novel eNpHR); 2)generation of redshifted excitatory optogenetic toolsto allow for deeper penetration of excitation light,use of well-tolerated low-energy photons forexcitation, and improved integration with existingCa2+ indicators; and 3) improved targetingstrategies to allow versatile cell type-specificexpression of the opsin genes in vivo.

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TMS, ERP and psychophysical experiments suggeststhis novel form of multisensory interaction maydepend on top-down visual modulation of localinhibitory interneurons in primary somatosensoryareas. Second, I will consider the bottom–uptransformation of primary somatosensory informationinto representations of external objects. Primarysomatosensory representations are optimised fortactile acuity, but their striking disproportions pose amajor computational challenge for the brain: how toreconstruct the true form of an external objectcontacting the skin from such non-uniform primaryrepresentations. I will suggest that the brain re-references primary inputs to a secondary mentalrepresentation of the body based on the true physicalsize of body parts. The nature and localisation ofthis second-level body representation, and its role inself-consciousness, are discussed.

NEURAL MECHANISMS OF SKYCOMPASS ORIENTATION IN AN INSECTUwe HombergPhilipps-Universität Marburg, Fachbereich Biologie,Tierphysiologie, D-35032 Marburg

Many insects use a celestial compass for spatialorientation and navigation. Several studies showedthat insects strongly rely on the polarization patternof the blue sky as a guiding cue but the position ofthe sun and the chromatic gradient in the sky offeruseful information, too. To elucidate the neuronalmechanisms underlying sky compass orientation,we have analyzed the polarization vision system inthe desert locust Schistocerca gregaria. As in otherinsect species, polarization vision in the desert locustrelies on specialized photoreceptor cells in a smalldorsal rim area of the compound eye. Thesephotoreceptors project to dorsal rim areas in thelamina and medulla. Central processing stages forpolarized light include the anterior optic tubercles,the central complex and surrounding areas in themedian protocerebrum. Most neurons showpolarization opponency, i.e. they receive excitatoryand inhibitory input from photoreceptors withorthogonal microvilli orientations. In the anterior optictubercle, polarized light sensitivity is combined withUV-green color coding mechanisms suggesting thatthese neurons code for solar azimuth by concurrentcombination of signals from the spectral gradient,intensity gradient and polarization pattern of the sky(Pfeiffer and Homberg, 2007, Current Biol 17:960).In the central complex, neurons combinepolarization-vision inputs from both eyes and havezenith-centered receptive fields. Single-cell recordingsrevealed a compass-like linear map of E-vector tuningsin the columns of the protocerebral bridge, asubcompartment of the central complex (Heinze andHomberg 2007, Science 315:995). Thisorganization suggests that the central complexcomputes and codes for azimuthal directions. This

may be used for azimuth-dependent recognition ofobjects in space as well as azimuth coding duringlong-range navigation.Supported by DFG grants HO 950/16-1 and 16-2.

ASTROCYTE REGULATION OF THECEREBROVASCULATUREBrian A. MacVicar1, Grant Gordon1, Hyun BeomChoi1, Sean J. Mulligan 21Brain Research Centre, University of British Columbia,Vancouver BC Canada 2Department of Physiology, Universityof Saskatchewan, Saskatoon SK, Canada

Astrocytes have recently been shown to be essentialparticipants in the control of cerebral blood flow(CBF) through their prominent control of cerebralvessel diameter. Although the unique closerelationship of astrocytes with cerebral blood vesselshas long been recognized it is only within the last fewyears that evidence has shown how astrocytes mighttranslate information to the vasculature on the activitylevel and energy demands of neurons. These findingssuggest that astrocytes are key players in the systemfor the delivery and clearance of molecules importantto brain function. Astrocytes possess the necessarysignaling capability to induce both vasoconstrictionas well as vasodilation in response to elevations inastrocyte endfeet Ca2+. Both types of vasomotorresponses are initiated by the generation ofarachidonic acid (AA) in astrocytes by Ca2+ sensitivephospholipase A2 (PLA2). Subsequent to AAformation, vasoconstriction occurs as a result of thegeneration of 20-hydroxyeicosatetraenoic acid (20-HETE), while vasodilation ensues from the productionof epoxyeicosatrienoic acid (EET) or prostaglandinE2 (PGE2). The primary drive to increase cerebralblood flow (CBF) is enhanced neuronal activity andmetabolic demands of brain tissue. However it isnot known if the metabolic state of the brain itselfinfluences the polarity of astrocyte control over thecerebrovasculature. Using two-photon Ca2+ imagingand uncaging as well as intrinsic nicotinamide adeninedinucleotide (NADH) imaging of single cells as ameasure of redox state, we have found that theability of astrocytes to induce vasodilations overvasoconstrictions critically relies on the glycolyticstate of the tissue which is altered by oxygen (O2)availability. Therefore the regulation of cerebral bloodvessels by astrocytes is in step with the metabolicneed of the surrounding brain tissue.Supported by a grant from the Canadian Institutes ofHealth Research, Heart and Stroke Foundation ofBC and Yukon, Canadian Stroke Network.

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IN VIVO IMAGING OF AXONREMODELINGThomas MisgeldTechnische Universität München, Institut fürNeurowissenschaften

The loss of axon branches is a shared feature ofneuronal development and of neurological disease.During development, dismantling of aberrant axonbranches is necessary to establish precise connectivity.Recurrence of axon loss in adult life, however, canlead to severe disability. The mechanisms that underliephysiological and pathological axon loss are notwell understood, but recent data support the notionthat nerve cells possess active machinery that allowsthem to selectively dismantle parts of their axon. Inour work, we have taken advantage of in vivomicroscopy of transgenic mouse lines withfluorescently labeled neurons to visualize how axonsdismantle during development and after injury. In mytalk, I will focus on our work on physiological axonloss at the developing neuromuscular junction, wherewe have identified ‘axosome shedding’ as a novelaxon loss mechanism. I will discuss data that showthat both the glial cells that surround doomed axonbranches, as well as axonal transport inside thesebranches might contribute to final dismantling. Ourdata suggest that local axon branch stability isdetermined both by interactions between neuronsand glial cells as well as by basic mechanisms ofaxonal resource allocation.

MODELLING OF COGNITIVE PROCESSESFelix A. WichmannTechnische Universität Berlin, FG Modellierung KognitiverProzesse

My group’s goal is to understand spatial vision and,ultimately, object and scene perception on abehavioral level. Helmholtz (1867) was perhaps thefirst to realize that visual perception is a form ofinference: visual percepts are hypotheses about theworld based on incomplete sensory evidence. Westrongly believe that progress towards understandingthis inference necessitates the combination ofpsychophysical experiments and computationalmodelling. Currently we have three main foci: First,we want to understand the initial coding of visualstimuli, the spatial and temporal dynamics of contrastgain-control, the form of spatial filters in early vision,and how this code is adapted to the characteristicsof natural stimuli. Second, we want to progress beyondearly vision and thus we need to infer the criticalstimulus features human observers use whenperceiving complex, natural scenes. To this end weare developing non- linear system identificationmethods based on machine learning to estimatepsychophysical perceptive fields from categorizationexperiments and eye-movement recordings. Third,once we have identified critical features, we want toaddress the fundamental problem of similarity and itsrelation to human categorization behavior: Can weformalize our intuitions about „similar“ objects? Isthere a psychological space spanned by the criticalfeatures in which stimuli are categorized as similar ifthey „live“ close together in it? In my brief talk at theBerlin Neuroscience Forum in 2008 I will concentrateon the second issue: to estimate psychophysical„receptive“ fields, so-called perceptive fields, fromthe fixation targets of free-viewing human observers.

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IMPLICATIONS FROM SYSTEMATICMETA-ANALYSES OF GENETIC ASSO-CIATION STUDIES OF ALZHEIMER’SDISEASE AND PARKINSON’S DISEASELars Bertram, MDGenetics and Aging Research Unit, Department of Neurology– Massachusetts General Hospital/Harvard Medical School,MassGeneral Institute for Neurodegenerative Disease(MIND), 114, 16th Street, Charlestown, MA 02129, USA

Background and Aims: Alzheimer’s disease (AD)and Parkinson’s disease (PD) are genetically complexand heterogeneous disorders. To date, a smallnumber of genes have been identified for bothdiseases causing predominantly early-onset formswith Mendelian inheritance. The majority of AD and

PD cases, however, show no obvious familialaggregation and are likely governed by a variety ofgenetic and non-genetic factors that define anindividual’s risk. In the past decade, literally hundredsof reports have been published claiming or refutinggenetic association between putative AD/PD genesand disease risk or other phenotypic variables, butonly a handful of these potential risk factors haveshown consistent effects over time.Methods: We have created two online databases thatserve as unbiased, continously updated and publiclyavailable collections of all AD or PD geneticassociation studies, including genome-wide analyses.Data is collected following systematic searches ofscientific literature databases, as well as the table ofcontents of speciality journals. For all polymorphisms

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with genotype data available in at least fourindependent case-control samples, we routinelycalculate meta-analyses based on allelic crude oddsratios from each study.Results and Conclusions: All data and results can beretrieved online (“AlzGene”: www.alzgene.org, and“PDGene”: www.pdgene.org). For both diseases, anumber of genetic variants have emerged to showsignificant risk effects in the meta-analyses. At themeeting, the most significant findings from bothdatabases will be highlighted, with a particular focuson genes/variants that concurrently modulate therisk for both disorders, potentially indicating commondenominators for neurodegeneration in AD and PD.

NEUROPROTECTION BY NOVELENDOGENOUS NON-HEMATOPOIETICERYTHROPOIETIN DERIVATIVESC. Bonnas1,2, A. Meisel1, J. Priller1,2

1Department of Experimental Neurology and 2Laboratory ofMolecular Psychiatry, Charité-Universitätsmedizin Berlin,10177 Berlin, Germany.

Hematopoietic cytokines have recently been identifiedas potent neuroprotective agents. Erythropoietin(EPO) is a glycopeptide hormone, which is primarilyproduced in the kidney. However, EPO is alsosynthesized in the brain by astrocytes, and EPO canprotect neurons from damage in various models ofneurological disorders. Unfortunately, clinical useof EPO as a neuroprotectant is complicated by itshematopoietic effects.We have identified endogenousEPO derivatives without hematopoietic activity. Incontrast to EPO, these EPO derivatives failed tostimulate erythropoiesis in clonogenic progenitorassays. However, both EPO and its derivativesprotected cultured rat neurons from oxygen-glucosedeprivation (OGD), an in vitro model of ischemia.EPO derivatives also protected H9C2 cardiomyocytesfrom OGD-induced cell death, suggesting that theyhave a more general cytoprotective potential. Wecharacterized the pharmacodynamics of EPO andits derivatives in vitro. Our data suggest that EPOderivatives are powerful neuroprotective agents, whichshare EPO’s cytoprotective effects, but do not showthe undesirable side-effect of promoting hema-topoiesis.

A TETHER LINK REQUIRED FOR TOUCHJing Hu, Li-Yang Chiang, Bettina Erdmann &Gary R. LewinMolecular Physiology of Somatic Sensation Group, MaxDelbrück Center for Molecular Medicine, Berlin, GermanyGenetic analysis of touch sensation in C. elegansand research on mechanosensitive hair cell in innercochlea have suggested the existence of anextracellular link which tethers the mechanosensitive

ion channels to matrix and transduces mechanicalforce to the channels (Ernstrom & Chalfie. 2002.Annu Rev Genet 36: 411-53; Syntichaki &Tavernarakis. 2004. Physiol Rev 84(4) 1097-153).So far there is no evidence showing whether in mousean extracellular link is essential formechanotransduction (Lewin & Moshourab. 2004.Neurobiol 61(1): 30-44). Recent evidence suggeststhat mechanotransduction components andmechanisms are conserved between C. elegans andmammals (Wetzel, Hu et al. 2007. Nature445(7124): 206-9). In the past few years we havebeen working intensively to address the questionwhether extracellular link is also conserved in mousemechanosensation. We have demonstrated that, asin C. elegans and Drosophila, an extracellular link isessential for mechanotransduction in mouse sensoryneurons. We have also found that cleaving this linkwith a serine endopeptidase-subtilisin couldimmediately and reversibly abolish themechanosensitivity of sensory neurons. This cleavageand regeneration of the extracellular link could beclearly observed using TEM (Transmission electronmicroscopy). This is the first evidence to show thatthe extracellular link of mechanotransducer existsand is essential for mechanosensation.

DIFFERENTIAL MECHANISMS UNDER-LYING ALTERED NEURONAL EXCITA-BILITY FOLLOWING BLOOD-BRAINBARRIER DISRUPTIONSebastian Ivens1, Yaron David2, Luisa P Flores3,Roxana Voitcu1, Daniela Kaufer3, UweHeinemann1, Alon Friedman1,2

1) Institut für Neurophysiologie, Charité UniversitätsmedizinBerlin, Germany; 2) Zlotowski Center for Neuroscience, Ben-Gurion University, Beer-Sheva, Israel; 3) Department ofIntegrative Biology, University of California, Berkeley, USA.

Perturbations in the integrity of the blood-brain barrierhave been reported in both humans and animalsunder numerous pathological conditions. Althoughthe blood-brain barrier prevents the penetration ofmany blood constituents into the brain extracellularspace, the effect of such perturbations on the brainfunction and their roles in the pathogenesis of corticaldiseases are unknown. In our work we established amodel for focal disruption of the blood-brain barrierin the rat cortex by direct application of bile salts.Exposure of the cerebral cortex in vivo to bile saltsresulted in long-lasting extravasation of serum albuminto the brain extracellular space and development ofa focus of epileptiform discharges within 4-7 d aftertreatment. We found that application of serum albuminto the cortex induced similar hyperexcitability withoutopening the BBB. Exposure of the cortex to serumalbumin is associated with albumin uptake intoastrocytes, which is mediated by transforming growthfactor beta receptors (TGF-betaRs). This uptake isfollowed by marked astrocytic activation and an

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altered pattern of astrocytic gene expression, as seenin microarray and rt-PCR analysis. We investigatedthe functional implications of altered expression ofgenes critically involved in the regulation of neuronalexcitability. Both, astrocytic potassium buffering andglutamate clearance were compromised and affectedneuronal function. To discriminate the effect of thetwo systems separately we used a neuron model andvaried both potassium and glutatmate clearance.While reduced potassium clearance lead to markedEPSC facilitation in stimulation trains, slowed glutamatetime constants had the opposite effect. However,both mechanisms together show a synergistic effect,leading to maximal EPSC facilitation maximal atstimulation frequencies of 10 Hz. Recordings frombrain slices exposed to albumin confirmed thisfrequency range. Our data suggests a crucial impactof astrocytic dysfunction on neuronal excitability andepileptogenesis following cortical albumin exposure.

MITOCHONDRIA AND NEURONALACTIVITY: INSIGHTS FROM THEHEALTHY AND THE EPILEPTICHIPPOCAMPUSOliver KannNeuronal Mitochondria Research Group, Institute forNeurophysiology, Charité – Universitätsmedizin Berlin,Germany

Mitochondria are central for various cellularprocesses that include ATP production andintracellular Ca2+ signalling. Neurons critically dependon mitochondrial functions to establish membraneexcitability and to execute the complex processes ofneurotransmission and plasticity. While muchinformation about mitochondria is available fromstudies on isolated mitochondria and dissociatedcell cultures, less is known about mitochondrialfunctions in intact neurons in brain tissue. In therecent years, my group has studied mitochondrialfunctions during neuronal activity in slice preparationsfrom the healthy and the epileptic hippocampus bycombining electrophysiological and imagingtechniques. We provide evidence 1) that there is afine-tuned coupling of neuronal activity andmitochondrial redox responses (energy metabolism),2) that rapid mitochondrial Ca2+ transients representone of the main determinants for neurometaboliccoupling, 3) that complex neuronal network activitiessuch as gamma-oscillations are highly sensitive todecreases in pO2 and concomitant changes inmitochondrial redox state, and 4) that the tight couplingof neuronal activity and mitochondrial functions hasdevastating consequences in epilepsy, which includeCa2+-mediated mitochondrial depolarization inneuronal dendrites and somas, formation of reactiveoxygen species (ROS) and subsequent metabolicdysfunction due to mitochondrial DNA and enzymedamage. Our studies highlight the importance of afunctional understanding of mitochondria duringactivities of individual neurons and neuronal networksin health and disease.

A VICIOUS CYCLE INVOLVING RELEASEOF HSP60 FROM INJURED CELLS ANDACTIVATION OF TLR4 MEDIATESNEURODEGENERATION IN THE CNSS. Lehnardt1, 2, E. Schott3, T. Trimbuch2, D.Laubisch2, C. Krueger2, G. Wulczyn2, R. Nitsch2,and J. Weber2

1Cecilie Vogt Clinic for Molecular Neurology in the HKBB,Charité-Universitaetsmedizin Berlin, 2Center of Anatomy,Institute for Cell Biology and Neurobiology, Charité-Universitaetsmedizin Berlin, 10117 Berlin, Germany, and3Department of Hepatology and Gastroenterology, CVK,Charité-Universitaetsmedizin Berlin, 13353 Berlin, Germany

Infection, ischemia, trauma, and neoplasia elicit asimilar inflammatory response in the central nervoussystem (CNS) characterized by activation ofmicroglia, the resident CNS monocyte. The molecularevents leading from CNS injury to the activation ofinnate immunity is not well understood. We showhere that the intracellular chaperone heat shockprotein 60 (HSP60) serves as a signal of CNS injuryby activating microglia through a toll-like receptor 4(TLR4)- and myeloid differentiation factor 88(MyD88)- dependent pathway. HSP60 is releasedfrom CNS cells undergoing necrotic or apoptoticcell death and specifically binds to microglia. HSP60-induced synthesis of neurotoxic nitric oxide bymicroglia is dependent on TLR4. HSP60 inducesextensive axonal loss and neuronal death in CNScultures from wild type but not TLR4 or MyD88 loss-of-function mutant mice. This is the first evidence ofan endogenous molecular pathway common tomany forms of neuronal injury that bi-directionallylinks CNS inflammation with neurodegeneration.

ALTERATIONS IN NEUROMETABOLIC-NEUROVASCULAR COUPLING BYCORTICAL SPREADING DEPRESSION INRAT SOMATOSENSORY CORTEXOffenhauser, N.; Böttiger, C.; Füchtemeier, M.;Royl, G.; Leithner, C.; Dirnagl, U.; Lindauer, U.Department of Experimental Neurology, Charité, Berlin

The mechanisms of activity induced changes incerebral blood flow (CBF) and metabolism areincompletely understood. We tested the hypothesisthat the relationship between evoked changes inneuronal activity, oxygen consumption and CBF isvariable and can be changed by cortical spreadingdepression (CSD). We investigated the effect of corticalspreading depression on functional activationinduced (forepaw stimulation) changes in neuronalactivity, rCBF and regional blood oxygenation (rCHO;oxy-, deoxyhemoglobin concentration) by SEPrecordings, laser-Doppler flowmetry and opticalhemoglobin spectroscopy in rat somatosensorycortex. Averaged responses prior to CSD werecompared with blocks of averaged responses up to1.5h after CSD. Baseline rCBF was transiently (~60

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min) reduced after CSD. This was accompanied byan increase in deoxy-hemoglobin (Hbr) and decreaseof oxy-hemoglobin (Hbo). Before CSD, activityinduced Hbr showed a well known isolated decreaseand Hbo changes were monophasic increases, whichfollowed the rCBF changes during activation. AfterCSD, rCBF responses and SEP were significantlyattenuated but tend to recover over time. The impactof CSD on evoked rCHO responses washeterogeneous. Hbr responses ranged from biphasicincrease-decrease patterns to entirely positiveresponses. At the same time Hbo increases weresignificantly attenuated, despite the recovering CBFresponse. Together, the individual parameters showeda different recovery pattern after CSD and suggest achange in the underlying energy metabolism duringactivation.The observed divergent modification ofactivity induced changes in rCBF, neuronal activityand blood oxygenation by a single CSD indicates along term (90 min) impairment of neurometabolic-vascular coupling and suggests a variable relationshipbetween neuronal activity and oxygen consumption,influenced by pathophysiological events.

PIGMENT EPITHELIUM DERIVED FACTORDURING POSTNATAL DEVELOPMENT,AGEING AND DISEASE OF THE NERVOUSSYSTEMPina AL., Kubitza M., Van Wagenen S., Ertl M.,Brawanski A.Department of Neurosurgery, Regensburg University Clinic,Regensburg, Germany

Pigment Epithelium Derived Factor (PEDF) is asecreted glycoprotein which possesses multiple andvaried biological properties, it is neurotrophic,neuroprotective, antitumorigenic and has a potentantiangiogenic activity. We have focused our attentionon exploring the specific localization, function andeffects of PEDF on the nervous system during normaldevelopment, aging, and disease. The following is abrief account of some of our results. We havedemonstrated that PEDF protein is naturally downregulated with age in the roedent eye and brain,leading to an increased VEGF/PEDF ratio with age.This suggests a potential higher risk forneovascularization and partly the cause of somedegenerative diseases at older stages of life in theseorgans. With Immunohistochemistry and cell specificdouble labeling we have shown the specificexpression of PEDF in endothelial cells and neuronsin various regions of the adult brain. This definedlocalization of PEDF open the possibility to searchfor other relevant effects of this factor in the brain.Our in vivo results show that intraventricular infusionof PEDF has a stimulatory influence on subventricularzone neural stem cells while reducing the proliferationof microglia cells in the traumatic injured brain. Theseresults support the importance of this molecule in

the control of neurogenesis and inflammation in thelesioned brain and indicate the significant therapeuticpotential that PEDF might have for the diseasednervous system.

A CGMP SIGNALING PATHWAYESSENTIAL FOR SENSORY AXONBIFURCATIONHannes Schmidt1, Agne Stonkute1, RenéJüttner1, Susanne Schäffer1, Jens Buttgereit2,Robert Feil3, Franz Hofmann3, and Fritz G.Rathjen1

1) Max Delbrück Centre for Molecular Medicine,Developmental Neurobiology Group, Berlin, Germany 2) MaxDelbrück Centre for Molecular Medicine, Molecular Biologyof Peptide Hormones Group, Berlin, Germany 3) TechnichalUniversity of Munich, Department of Pharmacology andToxicology, Munich, Germany

Axonal branching is a prerequisite for the formationof the complex wiring pattern of the mature nervoussystem E.g. the central trajectories of dorsal rootganglion axons display at least two types oframifications when they enter the spinal cord: (1)bifurcation at the dorsal root entry zone (DREZ) and(2) interstitial branching from stem axons to generatecollaterals that penetrate the grey matter. The signalingcascades that underlie axonal branching in vivo haveremained poorly understood thus far.We report a cGMP signaling cascade criticallyinvolved in the establishment of the highly stereotypedpattern of T-shaped axon bifurcation of sensory axonsat the DREZ of the spinal cord. Single axon labelingusing DiI revealed that embryonic mice with aninactive receptor guanylyl cyclase Npr2 or deficientfor cGMP-dependent protein kinase I (cGKI) lackthe bifurcation of sensory axons at the DREZ, i.e. theingrowing axon either turns rostrally or caudallyinstead. Cross-breeding experiments of these mutantmice with a mouse line expressing EGFP in sensoryneurons under control of the Thy-1 promoterdemonstrate that the bifurcation error is maintainedto mature stages. In contrast, interstitial branching ofcollaterals from primary stem axons remainsunaffected.At a functional level, the distorted axonal branchingis accompanied by reduced synaptic input, as revealedby patch clamp recordings of neurons in thesuperficial layers of the cord. Hence, our datademonstrate that a cGMP signaling cascade includingNpr2 and cGKI is essential for axonal bifurcation atthe DREZ and influences neuronal connectivity in thedorsal spinal cord.This work was supported by the DeutscheForschungsgemeinschaft (SFB 665)ReferencesSchmidt H, Stonkute A, Jüttner R, Schäffer S, ButtgereitJ, Feil R, Hofmann F, Rathjen FG (2007) The receptorguanylyl cyclase Npr2 is essential for sensory axonbifurcation within the spinal cord. J Cell Biol. 179:331-340.

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GENETIC DISSECTION OFSELENOPROTEIN FUNCTIONS INNEURONAL FUNCTION AND SURVIVALUlrich SchweizerNeurobiology of Selenium, Neuroscience Research Center,Charité-Universitätsmedizin Berlin

Selenoproteins (SePs) are a small, but significant,class of proteins containing the rare amino acid,selenocysteine (Sec). Although the functions of manySePs are still unknown, there is compelling evidencethat SePs carry out redox reactions like seleno-enzymes of the glutathione peroxidase (Gpx) andthioredoxin reductase (Txnrd) gene families. The braincontains low amounts of selenium (Se), but canmaintain its Se content even during prolonged Sedeficiency. Therefore, it is practically impossible tocreate an experimental model for brain Se deficiency.However, when we inactivated the selenoprotein P(SePP) gene, we destroyed the mechanism of brainSe retention. Accordingly, Sepp-KO mice are highlydependent on dietary Se uptake and suffer fromneurodegeneration and epilepsy at normally adequatedietary Se content. In an attempt to delineate whichcerebral cell type depends most on SeP expression,we created mice with neuron-specific ablation of thegene encoding tRNASec, thus preventing entirely SePbiosynthesis. Mice lacking neuronal SeP biosyntheticcapacity suffer from massive neurodegeneration inhippocampus and cerebral cortex from their secondweek of life. In culture, these neurons die even in thepresence of added antioxidants, suggesting that SePsmediate more than redox-control. We then geneticallydissected which single selenoproteins are necessaryfor neuronal function. While Gpx4 proved to be anindispensable gene, lack of Txnrd1 in neurons didnot cause neurological dysfunction. Recently,lipoprotein receptors (LRPs) have been identified asreceptors mediating SePP uptake. We found thatneurodegeneration observed in LRP-deficient mousemodels depends on dietary Se content raising thepossibility that compromised LRP function – asobserved in Alzheimer’s diesease – is not primarilycaused by disturbed cholesterin traffic, but by impairedSe uptake into the brain.

C-MAF IS AN IMPORTANT REGULATOROF MYELINATION IN THE PERIPHERALNERVOUS SYSTEMHagen Wende, Katja Reuter, Sandra Zurborg,Paul Heppenstall, Alistair Garratt and CarmenBirchmeierMax Delbrück Centrum für Molekulare Medizin (MDC)Berlin-Buch, Mouse Genetics, Berlin

The proto-oncogene c-Maf is a transcription factorof the basic-region leucine zipper (bZIP) family. c-Maf is known to control the differentiation of T cells,chondrocytes and the lens. c-Maf is also expressed

in the central and peripheral nervous system, but itsfunctions in neural cells have not been assessed. Weperformed a detailed analysis of c-Maf expression inthe nervous system, and observed that c-Maf isexpressed in glial cells of the peripheral nerves, andin a subset of sensory neurons. In Schwann cells, c-Maf expression is first detected around E18 and ismaintained in the adult. c-Maf expression is thusinitiated at the time Schwann cells start to myeliniate,and expression is observed in myelinating, but not innon-myelinating Schwann cells. c-Maf mutant micedie shortly after birth. To investigate by genetic methodsthe function of c-Maf in the peripheral nervous system,we introduced a targeted mutation using the Cre/loxP system and generated Wnt1-Cre//c-Maf mutantmice; such animals are viable. We observed in thesemutant mice a pronounced reduction in the myelinthickness of peripheral nerves. This hypomyelinationwas accompanied by the formation of tomaculae atthe nodes of Ranvier. In addition, the mutation of c-Maf leads to a reduced conduction velocity ofperipheral nerves. Despite this pronounced changesin myelination, we did not observe a change in theexpression of myelin genes. Our results demonstratethat c-Maf is an important factor in the transcriptionalnetwork regulating myelination in the peripheralnervous system.

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PPPPPoster Session Ioster Session Ioster Session Ioster Session Ioster Session I

ThursdayThursdayThursdayThursdayThursday, June 5, 15.35 - 17.00, June 5, 15.35 - 17.00, June 5, 15.35 - 17.00, June 5, 15.35 - 17.00, June 5, 15.35 - 17.00FFFFFridayridayridayridayriday, June 6, 10.00 - 11.00, June 6, 10.00 - 11.00, June 6, 10.00 - 11.00, June 6, 10.00 - 11.00, June 6, 10.00 - 11.00

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DETECTION OF SIGNALINGPATHWAY ACTIVATION IN RATDRG-NEURONS BY AUTOMATEDRELATIVEIMMUNOFLUORESCENCE

C. Andres, T. HuchoMax Planck Institute for Molecular Genetics, DepartmentRopers, Berlin, Germany

Posttranslational modifications are key to regulationof protein activity and can therefore be taken assurrogate measurement for the activity status ofsignaling proteins such as kinases. This is doneroutinely by the use of phospho-specific antibodiesin Western-Blot analysis or ELISAs. We now establishedin our laboratory a microscopy technique, whichanalyses the activation status based on single cellmeasurements in cultures of dissociated dorsal rootganglia from adult rats. For automatic identificationof neurons with an automated “Axioplan 2 imaging”(Zeiss) microscope controlled by the software“Metacyte” (MetaSystems), we optimised parametersdescribing form and size of neuronal cell bodies.Technical sources of variation such as bleachingand heterogeneous illumination of the view field wereminimized. Then, the immunofluorescence intensityderived from fluorophore-coupled phosphorylationspecific antibodies against signaling proteins wasmeasured in every single neuron. Comparing datafrom untreated and treated cultures, we were able tofollow induction of activation of the mitogen activatedkinases Erk1/2 and JNK as well as of the epsilonisoform of protein kinase C. The activation of thesesignaling pathways is known to be involved insensitization of nociceptive neurons. Therefore, thistechnique opens the door to automatedimmunofluorescent investigation of heterogenouscell systems such as nociceptive neurons evaluatingqualitatively for colocalization of proteins and/orsignaling events as well as quantitatively for themagnitude of activation of signaling cascades.

DEVELOPMENT OF GENETICTOOLS FOR SELECTIVE ANDREVERSIBLE SILENCING OF IONCHANNELS USING NATURALTOXINS

Auer, S.1; Jüttner, R.1; Ibanez-Tallon, I.Max-Delbrueck-Center for Molecular Medicine, CellularNeuroscience, Berlin, Germany,

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Venomous animals produce an enormous numberof different peptide toxins which often show a highaffinity for specific ion channels and receptors.Numerous of toxins from cone snails and snakeshave been reported to be selective as well as potentblockers of specific subtypes of ion channels(Albuquerque et al., 1997; Bowersox and Luther,1998; Nicke et al., 2003, 2004). Recently it hasbeen shown that these toxins retain their ability toblock ligand and voltage-gated receptors and ionchannels in Xenopus oocytes and in zebrafish whentethered to the cell surface via a GPI membraneanchor (Ibanez-Tallon et al., 2004). These toxinfusion constructs allow the genetic and cell-autonomous block of specific subsets of ionchannels and receptors after being expressed in thetarget cell. Our work combines the lentiviral systemfor tethered toxin delivery to the target cells and a tet-KRAB based, doxycycline inducible regulation ofexpression (Szulc et al., 2006), which together allowthe specific and also reversible silencing of receptorand ion channel subpopulations in a cell-autonomousmanner. To date we are testing several differentversions of tethered constructs with toxins targetingvoltage gated Ca2+-channels and nicotinicacetylcholine receptors on their functionality in-vitroin neuronal cultures as well as in-vivo in mice. In thefuture this new approach could be used to inhibitspecific currents in different brain regions and couldlead to more insight into the circuitory complexity ofthe brain, the way of information processing and theparticular contribution of single ion channel orreceptor subtypes.

A MODEL OF NEURONAL COLORCODING AND COLOR SENSATIONSIN MAN

Werner G. K. BackhausTheoretical and Experimental Biology, Neuroscience, FreieUniversity Berlin and University for Technology Berlin,Germany

Light entering the eye causes color sensations. Theelemental sensation spots consist of mixtures of thesix elementary color (EC) sensations red, green,blue yellow, black, and white [1] of the respectiveamounts, which are adequately detailed by thepsychophysical EC model. The neuronal color coding(CC) system is well described by the physiologicalCC model including physiological models of humancones [2]. The combined CC/EC model predictsthe amounts of elementary colors from the spectrallight intensity distribution alone.

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Classical psychophysical measurements [3] of theamounts of EC sensations, stimulated bymonochromatic light, were simulated with the CC/EC model. Best fits of predicted data to data measuredin two individual observers allowed for the uniquedetermination of the parameters. It turned out that thecolor vision system of observer II was most usual.Whereas observer I showed to possess an unusualblue/yellow color opponent coding (COC) neurontype, with two swapped excitatory and inhibitorysynapses. This result clearly demonstrates that theCC/EC model [4] enables even the identificationand localization of individual differences in neuronalcolor coding systems that are classified to be normaltrichromatic.[1]Hering, E., 1874. Zur Lehre vom Lichtsinne.Gerold, Wien.[2]Backhaus, W., 2006. Psychophysiologicalsimulations of spatial color vision. In: FünftesSymposium „Licht und Gesundheit“, 23.-24.2.2006,TU Berlin, Tagungsband, Hauptvorträge, pp. 8-21,Hrsg. H. Kaase & F. Serick. Kistmacher, Berlin.[3]Jameson, D. & Hurvich, L.M., 1955. Somequantitative aspects of an opponent-colors theory. I.Chromatic responses and spectral saturation, J. Opt.Soc. Am., 45, 546-552.[4]Backhaus, W. 2008. Psychophysiologicalsimulations of spatial color vision: II. Light and ColorSensations. In: Sechstes Symposium „Licht undGesundheit“, 13.-14.3.2008. Eine Sondertagungder TU Berlin und der DGP mit DAfP und LiTG, Hrsg.H. Kaase & F. Serick, Tagungsband, Hauptvorträge.Technische Universtät, Berlin (in press).

SODIUM CURRENTS IN IMMOR-TALIZED AND DEVELOPINGSTRIATAL PROGENITOR CELLS

Arne Battefeld, Ulrike Wasner, Beate Geist,Robert Nitsch, Ulf StraussCharité Universitätsmedizin Berlin, Centre for Anatomy,Institute for Cell- and NeurobiologyNa+ currents (INa) as key players in neuronaldevelopment have been studied in 3 different sets ofdeveloping rat striatal cells: (1) immortalized atembryonic day 14 (SV40 large T antigen transformedST14A) and short term cultured (2) at E14 and (3) atP0, using whole-cell patch-clamp, molecular andimmunocytochemical approaches. To investigate thepresence of voltage gated sodium channels we stainedwith a panNav antibody which confirmed theubiquitous presence and no differential distribution inall groups. However, in proliferating ST14A cellsfunctional INa was only present when held substantiallyhyperpolarised (-120 mV) in 26 out of 31 cells andirrespective of cell fate. INa activated with a V1/2 of-32 mV and showed a fast time- and voltage-dependentactivation and full inactivation. At a more physiologicalholding potential of -70 mV less INa was available(8/51) due to a remarkably hyperpolarised steady

state inactivation. INa in ST14A cells was TTX resistant.Current clamp experiments showed that INa can berecruited from a membrane potential below –90 mVand produce action potential like responses. E14and P0 striatal cells showed currents with similarkinetics, but a remarkable difference in availabilityand voltage dependence of activation of sodiumchannels and in their TTX sensitivity. The peculiarity inST14A might be explained by a relative overweightof “heart” NaV1.5 and especially its splice variantNaV1.5a as suggested by RT-PCR. We conclude thatNa+ channels are in the membrane of embryonicand early postnatal striatal cells, but they remainquiescent by a transcriptional mechanism. Alternativesplicing plays a role in regulation of functional INaand in the control of developmental state.

ALCOHOLISM MEDIATESASSOCIATION BETWEENSTRIATAL REWARD PROCESSINGAND IMPULSIVENESS

Anne Beck, Lorenz Deserno, Thorsten Kahnt,Jana Wrase, Andreas HeinzDepartment of Psychiatry and Psychotherapy, Charité -Universitätsmedizin Berlin, CCM

Alcoholism can be described as a well learnedbehavioral pattern, which is based upon biological,social and psychological factors. On aneurobiological level it may be connected withimpairments of the dopaminergic mesolimbic rewardsystem. Furthermore alcoholism might beaccompanied by altered personality factors likeimpulsiveness. Here we investigate the linkagebetween alcoholism, dysfunction in mesolimbicreward system and impulsiveness. Using functionalmagnetic resonance imaging (fMRI) we investigateddetoxified male alcoholics and age-matched healthycontrols during a monetary incentive delay task (MID).In this task, visual cues predicted that a rapid responseto a subsequent target stimulus would result in monetarygain, avoidance of monetary loss or noconsequence. Additionally the association withimpulsiveness was assessed using the BarrattImpulsiveness Scale (BIS). Alcoholics scoredsignificantly higher on the BIS than controls. Healthycontrols showed a significantly stronger activation ofventral striatum than alcoholics during bothanticipation of gain and loss. Additionally, in controls,BOLD response in putamen during gain anticipationwas negative correlated with impulsiveness. Incontrast, higher impulsiveness was associated withstronger BOLD response in putamen, anteriorcingulate and inferior frontal gyrus during anticipationof loss in alcoholics. These results support the notionof a dysfunction in the reward system in alcoholicsand elevated impulsiveness scores in these patients.Furthermore the negative correlation betweenactivation in putamen during reward anticipation andimpulsiveness in healthy controls was not observed

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in alcoholics. Instead, in alcoholics we found apositive correlation between activation in putamenduring loss anticipation and impulsiveness. Thesefindings suggest that alcoholism per se mediates therelationship between reward processing andimpulsiveness.

ROLE OF EXTRACELLULARSIGNAL-RELATED KINASE 1 IN THEREGULATION OF NEUROIN-FLAMMATION

I. Bendix, C.F. Pfueller, T. Leuenberger,V. Siffrin,U. Schulze-Topphoff, F. Zipp, S. WaicziesCecilie Vogt Clinic for Neurology in the HKBB, Charité -University Medicine Berlin, 10117 Berlin, and Max DelbrueckCenter for Molecular Medicine Berlin-Buch, 13125 Berlin,Germany

Extracellular signal-related kinases (Erk) are mitogen-activated protein kinases (MAPK) that are not onlyinvolved in T cell activation but are also known to beconversely involved in the induction of T cell anergy.Activation of the T cell receptor triggers amongstothers the Ras/Raf/MEK(MAPK Erk Kinase)/Erkpathway that controls the cell cycle machinery. Wehave shown that the 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitor atorvastatin inducesa sustained phosphorylation of Erk1 that is rathernecessary for atorvastatin-induced T cell anergy invitro. To determine the role of Erk1 in the inductionof peripheral tolerance in vivo we have induced EAE(experimental autoimmune encephalomyelitis) inErk1-/- C57BL/6 transgenic mice with a myelinoligodendrocyte glycoprotein peptide (MOG35-55).We show that Erk1 is important in regulating theprogression of the disease as shown by an increasedseverity and earlier development of symptoms in theErk1-/- mice. To dissect the role of Erk1 within theimmune versus the central nervous system we appliedbone marrow chimeras. For this we reconstitutedsublethally irradiated C57BL/6-CD45.2 mice withbone marrow cells of Erk1-/- or Erk+/+ (wildtypelittermate) C57BL/6-CD45.1 mice or alternativelyreconstituted sublethally irradiated Erk1-/- or Erk+/+

(wildtype littermate) C57BL/6-CD45.1 mice withbone marrow cells of C57BL/6-CD45.2 mice. Aftera minimum of 8 weeks we have induced EAE. Fromthese experiments we could clearly show that Erk1plays a predominant role in regulating an immuneresponse, as shown by a dramatic increased diseaseseverity in mice with an immune system deficient ofErk1. All together these results indicate the significanceof Erk1 in regulating immunological processes thatultimately lead to neuroinflammation and signal theimportance of therapeutically targeting this MAPKfor the treatment of autoimmune diseases.

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CLC-2 CL- CURRENTS IN OLIGO-DENDROCYTES FROM ACUTESLICES IN THE MOUSE CORPUSCALLOSUM

Bruno Benedetti*, Brigitte Haas**, Thomas J.Jentsch†, Helmut Kettenmann**Cellular Neuroscience, Max-Delbrück-Center for MolecularMedicine, Berlin, Germany **INSERM U840, College deFrance, Paris, France †Leibniz-Institut für Molekulare Phar-makologie im Forschungsverbund Berlin e. V., Berlin, Germany

Chloride channels have several roles in cellularphysiology including the control of water flux acrossthe membrane and cell volume regulation. In a recentstudy, Blanz et al. (2007) showed that the whitematter of the brain and spinal cord of ClC-2 knock-out mice developed widespread vacuolation betweenmyelin sheaths. ClC-2 is known to be expressed inastrocytes and neurons, but expression inoligodendrocytes has not been reported. Wetherefore recorded membrane currents with thepatch-clamp technique from oligodendrocytes inmouse corpus callosum in acute slices.Oligodendrocytes were identified by their typicalmorphology after injection with fluorescent dye troughthe electrode and their characteristic current profile.The cells had parallel processes in the orientation ofaxons tracts and currents elicited by de- andhyperpolarizing voltage steps showed fast decay andsymmetrical tails as previously described (Berger etal. 1991). To block the cationic components ofmembrane currents and isolate the ClC-2 current wesubstituted Na+ and K+ with NMDG and Cs+ in theextra- and intracellular solutions. In whole cellconfiguration, after dialysis, we stably recorded aninwardly rectifying, not inactivating current with a slowactivation kinetic. This current was reversibly blockedby to 300µM Cd++. These results are similar aspreviously reported for astrocytes (Makara et al.2003). This current component could not berecorded in oligodendrocytes from ClC-2-KO mice.We conclude that oligodendrocytes expressfunctional ClC-2 which seems to be important forthe maintenance of myelin.

SYNERGISTIC EFFECTS OF IL-4AND IL-10 ON AXONAL OUT-GROWTH AND REINNERVATION

Boato, F.1; Hechler, D.1; Rosenberger, K.1;Nitsch, R.1; Hendrix, S.1

1Institute for Cell Biology and Neurobiology, Center forAnatomy, Charité – Universitätsmedizin Berlin, GermanyControversial debate continues as to whether T cellsare able to promote central nervous system (CNS)repair. Evidence suggests that T-helper cells type 2(Th2) play a beneficial role in the context of CNSinjury. Recently, we could demonstrate that Th2 cellspromote axonal regeneration and functional recoveryafter CNS injury via perilesional delivery of interleukin-4 (IL-4). Here, we investigated the interaction of IL-4

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and IL-10 in axonal outgrowth and regeneration inorganotypic brain slices. Murine entorhinal cortex(EC) explants from p2 mice were embedded in athree dimensional collagen matrix. Axonal outgrowthwas analyzed after administration of IL-4, IL-10 or acombination of the two compared to untreatedcontrols. To more accurately analyze outgrowth inan in vivo context, we also tested the influence ofthese cytokines on the reinnervation of the denervatedtarget area by employing an organotypic co-culturemodel of enhanced green fluorescent protein(EGFP)-transgenic ECs and hippocampi. Using thesemodels, we were able to show that IL-4 and IL-10synergistically promote axonal outgrowth andreinnervation in organotypic brain slices.Furthermore, IL-10-induced axonal outgrowth oforganotypic brain slices is abolished in slices derivedfrom IL-4 receptor-deficient mice, while IL-4 secretedby transfected fibroblasts did not promote axonaloutgrowth in the absence of IL-10. These datasuggest, that IL-10-induced axonal outgrowth isdependent on IL-4 receptor signaling.

MIGRATION OF GENE-MODIFIEDBONE MARROW-DERIVED CELLSINTO MOUSE RETINAS

C. Boettcher1, S. Beck2, R. Bauer2, M. W.Seeliger2, J. Priller1

1 Laboratory of Molecular Psychiatry, Charite´-Universitäts-medizin, Berlin, Germany, 2 Institute for Ophthalmic Research,University of Tübingen, Germany

Bone marrow-derived cells (BMDCs) have beensuggested as a delivery system for gene therapy inretinal degenerations. The potential of BMDCs fortransferring a therapeutic gene into the CNS is yetcontroversial. To study the migration of BMDCs intothe retina, EGFP-expressing BMDCs were systemicallytransplanted into lethally irradiated C57BL/6 recipients.Irradiation-induced functional and morphologicalchanges of the retina were estimated at 5 and 12weeks post-BM transplantation (pBMT) by scanninglaser ophthalmology (SLO) and electroretinography(ERG). The time-dependent induction of cytokineand chemokines in the irradiated eyes was determinedover 12 weeks pBMT. Chimeras were killed at 1, 2,4, 12, 32, 44 and 60 weeks pBMT. The retinaswere analysed by immunohistochemistry. To provethe efficacy of BMDCs for gene delivery into theretina, retrovirally transduced BMDCs expressingEGFP were transplanted to lethally irradiated mutantrecipients with retinal degenerations (SCA7 and FVB/N). The retinas were analysed at 8 and 12 monthspBMT. Over 3 months pBMT, irradiation-inducedfunctional and morphological alterations of the retinawere not significantly observed. The induction ofchemokine and cytokine appears to coincide withthe appearance of EGFP-expressing microglia in theeyes. EGFP-expressing cells in retinas were identifiedas microglia based on morphology and

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immunophenotype. The number of GFP-expressingretinal microglia was not significantly changed after32 weeks pBMT. In mutant retinas, gene-modifiedBMDCs were found to persist for up to 1 year pBMTwith a stable expression of EGFP from a retrovirus.Taken together, BMDCs may be used as vehicles forgene delivery to the retina.Supported by a grant of the Deutsche Forschungs-gemeinschaft to JP.

MECHANISMS AND FUNCTIONALROLE OF IMMUNE RESPONSEFOLLOWING AXONAL LESION

Brandt, C1.; Meisel, C2.; Richter, D1.; Ellinghaus,A1.; Bechmann, I3.; Nitsch, R1.1Center for Anatomy, Institute for Cell Biology undNeurobiology, Charité – Universitätsmedizin Berlin; 2Institut ofImmunology, Charité - Universitätsmedizin Berlin; 3Institute ofClinical Neuroanatomy, J.W. Goethe-University, Frankfurt/Main.ECL-induced brain damage does not involve a typicaladaptive immune response. However, ECL leads tothe activation of microglia migrating to the zones ofaxonal degeneration where they act asimmunophenotypically antigen-presenting cells(MHCII+, CD86+, CD80-) and come into closecontact with infiltrating T cells. It has been observedthat initial expansion of myelin-specific T cells andsubsequent inflammation in regions of axonaldegeneration are transient and presumably regulated,implying an active maintenance of immune tolerance.We have found that mice pre-treated with ECL 30days before EAE induction show a reduced EAEdisease severity, indicating that an immune responsetriggered by traumatic injury may induce regulatoryimmune mechanisms. Moreover we could show thatmicroglia induce regulatory T cells in an antigen-specific manner in vitro. Furthermore, traumatic CNSinjury such as ECL induces an increased number ofregulatory T cells in the brain in a time-dependentfashion in vivo.Taken together, these data suggestthat microglia are involved in the development andinduction of regulatory immune mechanisms in thecontext of CNS trauma. Elucidating the role ofmicroglia-primed T cells in CNS trauma may lead toa better understanding of general mechanisms inneuroregeneration.

B56ß INTERACTS WITH CALEB/NGC AND INHIBITS CALEB/NGC-MEDIATED DENDRITIC BRANCHING

N. Brandt, R. Nitsch, and S. SchumacherInstitute of Cell Biology and Neurobiology, Center for Anatomy,Charité – Universitätsmedizin Berlin, Charitéplatz 1, D-10117Berlin, Germany.

The development of dendritic arbors is essential forneuronal information processing, but the underlying

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mechanisms are currently not well understood. Theimportance of transmembrane proteins forconnecting extrinsic cues, which regulate dendriteformation, to intracellular mediators of cytoskeletalrearrangements has been highlighted during the lastyears. Recently we demonstrated that CALEB/NGC(Chicken Acidic Leucine-rich EGF-like domaincontaining Brain protein/Neuroglycan C), a neuralmember of the EGF family, is a critical mediator inthe formation of dendritic tree complexity byenhancing dendritic branching. Here we show a moredetailed characterization of the mechanismsunderlying CALEB/NGC-induced dendritic branching.Extracellularly, the EGF-like domain of CALEB/NGCis necessary and sufficient for stimulating dendriticarborization. In a screen for novel interaction partnersof CALEB/NGC, which functionally link thistransmembrane protein to the phosphatidylinositide3-kinase-Akt-mammalian target of rapamycinpathway, we identified B56ß, a regulatory subunit ofprotein phosphatase 2A, as a candidate thatnegatively regulates CALEB/NGC-induced dendriticbranching.Literatur:Brandt et al., 2007 EMBO J 26, 2371-2386Brandt et al., 2008 FASEB J, accepted

LATERAL LINE RESPONSES INTE-GRATE THE WAVE CURVATURE

F. Branoner, U. Ziehm, Z. Zhivkov, C. Schuldtand O. BehrendAquatic Bioacoustics Lab, Institute of Biology, HumboldtUniversity Berlin, Germany

Xenopus laevis uses a mechano-sensory lateral linesystem for localizing prey on the water surface. About180 water-velocity sensitive organs (‘stitches’) aresystematically distributed at the frog’s body andencode wave signals. Excitation patterns across thesestitches are used to compute wave sourcerepresentations in the CNS. In this study the effectsof the wave curvature on the responses in the CNSwere investigated. Three wave sources were placedin 4.5, 6.75 and 9 cm (corresponding wavecurvatures were 22.2, 14.8 and 11.1 m-1).Standardised stimulus paradigms were used and waveamplitudes and spectral composition were stabilizedat the frog’s centre. 98 responses to surface wavestimuli were extracellularly recorded. Wavefrequencies eliciting best response peaked at 30 Hz(26% of all units). Stimulation of the frog from variousdistances (resulting in variable wave curvatures) withstabilized surface waves (in terms of amplitude andfrequency) elicited significant curvature-dependentresponse rates for 60 of 98 central LL-units (p<0.05;Wilcoxon-test). 75% of these units displayed aresponse-rate change >50% when stimulated fromthe 3 source distances. 8 out of 38 LL-units showedno distance-sensitivity based on response-rate butphase coupling for a subset of wave sources only

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(Rayleigh test, p<0.05; VS>0.03). Combined, 69%of the 98 recorded units showed changes in thereresponse rate or their VS and were considered asdistance sensitive. Additional studies were initiated toinvestigate the influence of different stimulation angleson the responses in the CNS. Two sets of wavesources (3 distances each) were placed at 90° and0° relative to the frog’s rostro-caudal axis. Of 8recorded distance sensitive units, 6 exhibited the sametrend in their rate-curvature functions at bothstimulation angles – suggesting stable distance codingmight occur in the CNS based on wave curvature.

DYSFERLIN DEFICIENT MUSCULARDYSTROPHY FEATURESAMYLOIDOSIS

Miriam Carl1, Joanna Zabojszcza1, Kate Bushby2,Steven A. Moore3, Christoph Röcken4, SimoneSpuler1

1Muscle Research Unit, Experimental and Clinical ResearchCenter at the Charité and the Max-Delbrück Center, Berlin,Germany ; 2Institute of Human Genetics, University ofNewcastle upon Tyne, UK, 3Institute of Neuropathology, RoyJ. and Lucille A. Carver College of Medicine, University ofIowa Hospitals and Clinics, Iowa City, IA, USA; 4Dept. ofPathology, Charité, Berlin

Objectives: Dysferlin is widely expressed and hasbeen implicated in diseases such as multiple sclerosisand Alzheimer disease. Mutations in the dysferlingene (DYSF) cause muscular dystrophy (LGMD2B,Miyoshi-myopathy). The consequences of DYSFmutations on protein structure are poorly understood.Methods: The gene encoding dysferlin was sequencedin patients with suspected dysferlin-deficient musculardystrophy. Muscle biopsy specimens were analysedby histochemistry, immunohistochemistry andelectron microscopy. Antibodies against N-terminaldysferlin-peptides were raised.Results: In three families with homozygous orcompound heterozygous DYSF mutations widespreadamyloid deposits were detected in skeletal muscle.Known causes of amyloidosis were excluded anddysferlin was identified as a main constituent of theamyloid deposits. Mutations in DYSF leading toamyloid are all located within the same region of thegene.Conclusions: LGMD2B is the first muscular dystrophyassociated with amyloidosis and dysferlin is a newamyloidogenic protein.

ROLE OF GALPHA-I-2 ON ZO-1 UNDEREPINEPHRINE STIMULATION

V. Castro Villela1, M. Sing Bal1, J. Piontek1, C.Rückert1, B. Nürnberg2, I. E. Blasig1

1Leibniz-Institut für Molekulare Pharmakologie; Berlin; 2Max-Delbrück-Center for Molecular Medicine, Berlin; UniversitätDüsseldorf

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The blood-brain-barrier permeability in several brainpathologies is increased, leading to complicationsand decreasing survival. Tight Junctions (TJ) areprotein complexes in endothelial/epithelial cellmembranes attaching cells to each other, sealing theparacellular cleft and regulating its permeability. Thescaffolding protein of TJ is ZO-1. Its SH3 and GuKdomains form a functional SH3-hinge-GUK unit(ShG) that binds other junctional proteins and can bephosphorylated. TJ are indirectly regulated by G-protein-signaling cascades: Gα0 and Gαi2 may increaseTJ biogenesis and paracellular tightness respectively,and a constitutively active mutant of Gα12 reduces theparacellular tightness. We propose a direct bindingof Gαi2 to the ShG unit of ZO-1. HEK-293 cellswere cotransfected with CFP-Gi2 and one of thefollowing: ZO-1(ZO1YFP), C-terminal-truncated ZO-1(ZO117-899YFP) or ShG(YFPZO1520-809). After 72 h,the cells were incubated in 5, 50 and 500µMepinephrine for 10 min, and fixed for LSCM analysis.Same cotransfections were spectrofluorometricallyassayed for FRET. Our preliminary data show thatafter cotransfection with CFP-Gαi2 the ZO1YFPexpression is enriched at the cell-cell contactsacquiring an epithelial-like pattern. Under 5 µMepinephrine, Gi2 shifts its intracellular distributionfrom the cytosol to the submembranal spacecolocalizing with ZO1YFP. Partial colocalization withZO117-899YFP and YFPZO1520-809(ShG) is always observed,but is increased after 5 µM epinephrine stimulation.The fluorescence spectra under non-stimulatingconditions showed mild FRET in all cases, but theirefficiency increased after 5µM epinephrinestimulation. These results suggest that Gi2 can binddirectly to the ShG unit of ZO-1 and might facilitatemembrane localization of ZO-1, probablyrepresenting a first-response modulator of TJ,triggered after cell stress or pharmacologicalintervention.

PERSONALITY TRAITS ANDSTRUCTURAL BRAIN ALTERA-TIONS IN HEALTHY SUBJECTS: AMORPHOMETRIC ANALYSIS OFMRI-DATA

K. Charlet1, Y. Gudlowski1, C. Kaufmann2, F.Schubert3, A. Heinz1 and J. Gallinat1

1Department of Psychiatry and Psychotherapy Campus Mitte,Charité University Medicine, Berlin, Germany, 2Department ofPsychology, Humboldt-University zu Berlin, Berlin, Germany,3Physikalisch-Technische Bundesanstalt, Berlin, Germany

Various neuroimaging studies draw an associationbetween genetics, personality and structural brainalterations. For example, surveys examining normalfear conditioning or psychiatric disorders (e.g. anxietydisorders, mood disorders) demonstrated agenetically driven fear-processing network, involvingsubcortical structures and prefrontal neocorticalareas. Identifying such associations in healthy subjects

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might help to understand human behavior and mayhelp in the early detection and treatment of mentaldisorders. This investigation aimed for the detectionof such specific processing patterns determined bypersonality traits, behavioural parameters and geneticpredispositions. We examined the correlation betweengray matter volume on a voxel-by-voxel basis usinghigh-resolution T1-weighted magnetic resonanceimage (MRI) and optimized voxel-based morphometry(VBM) analysis and personality parameters, such asanxiety, sensation seeking, neuroticism in healthysubjects in fourty-six healthy subjects. Major personalitytraits were correlated with gray matter volume in theprefrontal and orbitofrontal lobe suggesting a keyrole of the frontal lobe in behavioral control andsocial competence. Gray matter volume of additionalcerebral regions showed significant correlations withpersonality traits indicating a broad neuronal networkinvolved in normal human behavior. Furthermore,the impact of genetic variations of neurotransmittersystems implicated in behavioral modulations oncerebral morphometry will be presented.Supported by a grant of the Universitäre Forschungs-förderung, Charité Universitätsmedizin Berlin.

AMEBOID MICROGLIA INDEVELOPING BRAIN INDIRECTLYRESPOND TO GABA- ANDGLUTAMATERGIC ACTIVITIES BYSENSING THE RESULTINGINCREASE IN EXTRACELLULARPOTASSIUM.

Giselle Cheung, Oliver Kann1, Katrin Färber,Helmut KettenmannCellular Neuroscience, Max-Delbrück-Center for MolecularMedicine, Berlin, Germany, 1Institute for Neurophysiology,Charité – Universitätsmedizin Berlin, GermanyMicroglial cells invade the brain during early postnataldevelopment, migrate preferentially along fiber tractsto their final position and transform from the ameboidto a ramified form. Signals by which theycommunicate with other brain cells are largelyunknown at this early developmental stage. In thepresent study, we studied ameboid microglia inpostnatal corpus callosum which accumulated onthe surface of acute brain slices obtained from 6-8days old NMRI mice. Whole-cell patch clamprecordings from microglia revealed that both, GABAand glutamate trigger an increase in the inward K+

conductance. When microglial cells were removedfrom the slice surface, the effect of GABA andglutamate was abolished indicating that microglia donot respond directly to GABA and glutamate. A likelycandidate for the direct signal to microglia is K+]0since an increase in K+]0 mimics the response toGABA and glutamate and extracellular K+

measurements indicating that both transmitters triggersuch an increase. While increased [K+]0 has noeffect on microglial chemotaxis and proliferation,

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basal release of macrophage inflammatory protein-1 alpha (MIP-1apha, also termedCCL3) wasenhanced in situ and in primary microglial cultures.Our results indicate that invading microglia in earlypostnatal brain can sense GABAergic andglutamatergic signaling indirectly via sensing changesin [K+]0.

ROLE OF EXTRACELLULARMATRIX IN SENSORY MECHANO-TRANSDUCTION

Li-Yang Chiang, Jing Hu, Bettina Erdmann,*Manuel Koch & Gary R. LewinMolecular Physiology of Somatic Sensation Group, MaxDelbrück Center for Molecular Medicine, Berlin. *Center forBiochemistry and Department of Dermatology, Medical Faculty,University of Cologne

Genetic screens carried out in both Caenorhabditiselegans (C. elegans) and Drosophila Melanogasterhave suggested that extracellular proteins might beessential for the transducton of body touch and flybristle movement respectively (Chung et al. 2001.Neuron 29: 415-28; Du et al. 1996. Neuron 16:183-94; Ernstrom & Chalfie. 2002. Annu Rev Genet36: 411-53). There is no direct evidence thatextracellular factors are crucial for the gating ofsomatic mechanotransduction channels invertebrates. In order to investigate this, we haveestablished co-cultures of sensory neurons and skin-derived keratinocytes or fibroblasts. We have askedwhether different extracellular environments modifythe transduction of mechanical stimuli by DRGneurons. In this project, we have found the molecularnature of the extracellular environment canprofoundly modulate mechanosensitive channels inDRG neurons. Matrix derived from keratinocytes hasprofoundly inhibitory effect on mechanosensitive RAcurrents. It has been shown Laminin5 is exclusivelyexpressed in Keratinocytes. We found Laminin5containing matrix can reproduce the inhibitoryproperties of keratinocytes matrix on DRGmechanosensitivity. Future experiments with laminin5deficient matrix will allow us to determine if Lamnin5itself is inhibitory.

MODULATION OF NEURONALMEMBRANE PROPERTIES BY THECOXSACKIEVIRUS-ADENOVIRUSRECEPTOR

Cholewa J., Jüttner R. and F. G.RathjenMax Delbrück Center for Molecular Medicine, BerlinThe coxackie virus and adenovirus receptor (CAR)was originally identified as a cell surface proteinenabling both viruses to interact with cells. Besidesthis pathological role as a virus receptor, thephysiological function in the CNS is largely unknown.

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CAR is a member of the Ig superfamily composedof two Ig-like domains, a transmembrane stretchand a cytoplasmic segment. CAR is expressed earlyin development on neurons and becomes restrictedto synapse-rich layers at more advanced stages.Application of the fiber knob of the adenovirus,which binds to CAR, resulted in longer neurites incomparison to the untreated cell cultures.Furthermore, the formation of cell aggregates wasreduced by the fiber knob. By using whole-cell patchclamp technique we analyzed the effect of the fiberknob on passive membrane properties and synapticactivity. The fiber knob was able to reduce themembrane resistance (Rm). Consistently, in CARdeficient neurons Rm was significantly highercompared to wild type neurons, and application offiber knob had no effect on Rm on CAR-deficientneurons. Thus, CAR may influence Rm via membraneproteins with a membrane conductance. Gap junctionproteins form large pores with a high permeabilityand might therefore be candidate proteins regulatedby CAR and the fiber knob. In line with this hypothesis,application of different connexin blockers results ina significant increase in Rm in wild type but not in CARdeficient neurons. As a consequence of the absenceof CAR, which seems to be essential for the regulardevelopment, synaptic connectivity was diminished,as shown by reduced frequency of inhibitorypostsynaptic currents. Our results suggest that CARmight influence membrane resistance by modulatingthe function of gap junctions. As a consequence forimpaired electrical coupling in the CAR deficientneurons, formation of synaptic circuits is reduced.

PRG-5 IN CULTURED NEURONSINDUCTS DENDRITIC-SPINEFORMATION

P. Coiro, T. Velmans and A. U. BräuerCharité, Centre of Anatomy, Institute for Cell- andNeurobiology Philippstraße 12, 10115 Berlin

Dendritic spines are small protrusions off the dendritethat receive excitatory synaptic input. In the developingbrain, spines show highly dynamic behaviour thoughtto facilitate the formation of new synaptic contacts.Here, we report that the six transmembrane proteinplasticity related gene 5 (PRG-5), a new member ofthe PRG family, which defined a novel sub-class ofthe LPP super family, induces dramatic morphologicalrearrangement in HEK cells and promotes theformation of spines in cultured neurons from mousebrain. PRG-5 is high expressed in the brain and showsa specific expression pattern during braindevelopment where PRG-5 expression is alreadydetected at embryonic day 14. PRG-5 contains threedomains on the extra cellular loops, named C1, C2and C3 with high sequence homologies to the aminoacids residues of the LPP family members. The threedomains in LPP members are responsible of theectophosphatase activity. Mutagenesis experiments

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in PRG-5 have shown a possible role for residueswithin the domain C2 and C3, that are crucial forinduction of spines. These observations suggest thatPRG-5 may be a novel integral membrane proteininvolved in regulating dendritic-spine morphology bya “catalytic domain” detected in both C2 and C3protein domains.This study is supported by the DFG (BR 2345/11-1)and NäFog-stipendium for P. Coiro

DEVELOPMENTALLY REGULATEDEXPRESSION, LOCALIZATION ANDFUNCTIONAL REGULATION OFCALEB, AN EGF-LIKE PROTEIN

Craveiro, R.B., Jüttner, R. and Rathjen, F.G.Developmental Neurobiology, Max-Delbrueck-Center forMolecular Medicine, Berlin

The establishment of precise and selective synapticconnections between neurons during embryonic andearly postnatal development depends on thecoordinated interplay of an orchestra of molecularcomponents. One these components is CALEB(ccccchicken aaaaacidic llllleucine-rich EEEEEGF-like domaincontaining bbbbbrain protein), a transmembrane protein.Due to its structural features, it belongs to the EGF-family. It was shown that CALEB is converted byneuronal activity and involved in regulating neuronalconnectivity early in development. Analysis of theexpression of CALEB by immunohistochemistry,immunoblot and RT-PCR showed that it is restrictedto the central nervous system. It appeared inembryonic and early neonatal stages in developmentand expression peaks between postnatal day 10 and20, a period of synaptogenesis and synapserefinement. Subcellular localization of CALEB studiedby bio- and immunocytochemical methods indissociated neuronal cell cultures revealed that CALEBis predominantly located in plasma membranes ofdendrites and cell bodies, but not in axons. Doubleimmunostaining of CALEB together with pre- orpostsynaptic proteins provided evidence for a partiallocalization on synapses. Protein phosphorylationand dephosphorylation are pivotal steps in signaltransduction and play a key role in the regulation ofmany cellular processes. Therefore, potentialPhosphorylation sites of CALEB were analyzed bymass spectroscopy. In summary, the developmentallyregulated expression pattern and localization ofCALEB supported our physiological studies andsuggests that CALEB is implicated in the formation ofneuronal circuits.

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21 COMPLEMENTARY CONTRIBU-TIONS OF PREFRONTAL NEURONCLASSES IN ABSTRACT NUME-RICAL CATEGORIZATION

Diester, IlkaHertie Institute for Clinical Brain research, CognitiveNeurology, Otfried-Müller-Str. 27, 72074 Tübingen

A variety of neuronal classes build the basis of thecortex, but their contributions to cathegoricalknowledge has remained unclear. We found thatextracellular recorded waveforms from macaqueprefrontal cortex can be separated into twosubpopulations. One subpopulation is characterizedby narrow spike waveforms and shares many featureswith inhibitory interneurons whereas the features ofthe other subpopulation resemble those of pyramidalcells. In a cognitively demanding numerositydiscimination task, the neuron classes followeddifferent encoding schemes. Whereas the putativeinterneurons were recruited with a high reliability ofstimulus discrimination but with low stimulus selectivity,the putative pyramidal cells encoded numerical valueshighly specifically. These findings argue for a devisionof labor between neuron classes in a feedforwarddesign in which interneurons contribute highly reliableinformation across a broad range of stimuli whereaspyramidal cells could represent a more definitestimulus representation one step further in thedecision process.

ALPHA-1A ADRENERGIC RECEP-TORS REGULATE NEUROGENESISAND COGNITIVE FUNCTION

Doze, V.; Boese, S.; Knudson, C.; Goldenstein,B.; Schlosser, D.; Carr, P.; Perez, D.1Pharmacology, Physiology & Therapeutics, 2Anatomy & CellBiology, University of North Dakota, Grand Forks, ND,3Molecular Cardiology, The Cleveland Clinic, Cleveland, OH

Neurogenesis has potential as a treatment for epilepsyand neurodegeneration. The endogenousneurotransmitter norepinephrine (NE) may beinvolved in promoting neurogenesis through theactivation of alpha-1A adrenergic receptors (α1A-ARs). However, our understanding of the α1A-ARfunction has been limited due to a lack of specificligands and antibodies. To address this, transgenicmice were generated which over-express the α1A-ARwith enhanced green fluorescent protein (EGFP) orconstitutively active mutant (CAM) α1A-ARs. Knockout(KO) α1A mice were also generated. Immuno-histochemistry showed that CAM α1A-AR mice hadincreased BrdU incorporation in vivo in thesubventricular zone (SVZ) compared to normal. CAMα1A and α1A-AR-EGFP had increased numbers ofhippocampal interneurons compared to normal andKO α1A-AR. Increased numbers of interneurons mayaffect certain cognitive processes such as learning

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and memory as well as seizure susceptibility. To assesscognitive function, normal, α1A-AR-EGFP, CAM α1A,and KO α1A-AR mice were tested using the multi-component T-, Morris water and Barnes mazes. CAMα1A and α1A-AR-EGFP mice displayed enhancedcognitive abilities compared to normal mice. In allmazes, KO α1A-AR mice displayed the worst cognitivefunction. Treating normal mice with the selective α1A-AR agonist cirazoline also showed enhanced learningand memory processes. Furthermore, when treatedwith the epileptogenic agent flurothyl, CAM α1A andα1A-AR-EGFP mice showed an increase in latencyperiods preceding seizures compared to normal mice.These results suggest that stimulation of α1A-ARs mayoffer a new therapeutic strategy for increasingcognitive function and treating neurodegenerativediseases. Supported by ND EPSCoR EPS-0447679,NSF CAREER 0347259, and NIH COBREP20RR017699.

‘NORMAL’ AND ‘INVERSE’ NEURO-VASCULAR COUPLING AND SUP-PRESSION OF LOW-FREQUENCYVASCULAR FLUCTUATIONSDURING CORTICAL SPREADINGDEPOLARISATION IN THE HUMANBRAIN

Dreier, J.P.; Major, S.; Manning, A.; Woitzik J.;Drenckhahn, C.; Steinbrink, J.; Tolias C.;Einhäupl, K.M.; Fabricius, M.; Hartings, J.A.;Vajkoczy, P.; Lauritzen, M.; Dirnagl U.; Bohner,G.; Strong,Charité University Medicine Berlin, Neurology, 10117 Berlin

The term ‘default mode’ describes the process thatthe brain remains active in an organised fashionduring rest. Low-frequency fluctuations of regionalcerebral blood flow (rCBF) reflect neurovascularcoupling in the ‘default mode’. Cortical spreadingdepolarisations (CSD) suppress the restingelectrocorticographic activity and, thus, disrupt the‘default mode’. Neurovascular coupling during CSDis either characterised by transient hyperperfusionunder normal conditions or is ‘inverse’ andcharacterised by marked hypoperfusion in tissue atrisk of progressive damage. Here, we performed aprospective study assessing neurovascular couplingduring CSD in ten patients with stroke or traumaticbrain injury. Simultaneous recordings of rCBF withlaser-Doppler flowmetry and the electrocorticogramusing subdural opto-/electrode strips revealed thatCSD shows the full spectrum from ‘normal’ to‘inverse’ neurovascular coupling and attenuation oflow-frequency vascular fluctuations in the humanbrain. The option for a novel ‘functional marker’ ofprogressive ischaemic brain damage is suggestedobservable by vascular imaging techniques. ‘Inverse’coupling is suggested as a novel target for treatmentdevelopment.

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24 GLYCINERGIC TONIC INHIBITIONOF HIPPOCAMPAL NEURONSWITH DEPOLARISING GABAERGICTRANSMISSION ELICITS HISTO-PATHOLOGICAL SIGNS OFTEMPORAL LOBE EPILEPSY

Sabrina A. Eichler1, Sergei Kirischuk2, RenéJüttner3, Philipp K. Schäfermeier1, PascalLegendre4, Thomas-Nicolas Lehmann5, TengisGloveli6, Rosemarie Grantyn2, Jochen C. Meier1,7

1RNA Editing and Hyperexcitability Disorders HelmholtzGroup, Max Delbrück Center for Molecular Medicine, Berlin,Germany, 2Developmental Physiology, Institute forNeurophysiology, Charité University Medicine Berlin,Germany, 3Developmental Neurobiology, Max DelbrückCenter for Molecular Medicine, Berlin, Germany, 4UMRCNRS 7102 NPA, Université Pierre et Marie Curie, Paris,France, 5Department of Neurosurgery, Charité UniversityMedicine Berlin, Germany, 6Cellular and Network Physiology,Institute of Neurophysiology, Charité University MedicineBerlin, Germany

An increasing number of epilepsy patients are afflictedwith drug-resistant temporal lobe epilepsy (TLE) andrequire alternative therapeutic approaches. High-affinity glycine receptors (haGlyRs) are functionallyadapted to tonic inhibition due to their response tohippocampal ambient glycine, and their synthesis isactivity-dependent. Therefore, in our study, we scannedTLE hippocampectomies for expression of haGlyRsand characterised the effects mediated by thesereceptors using primary hippocampal neurons.Increased haGlyR expression occurred in TLEhippocampi obtained from patients with a severecourse of disease. Furthermore, in TLE patients,haGlyR and KCC2 expressions were inverselyregulated. To examine this potential causalrelationship with respect to TLE histopathology, weestablished a hippocampal cell culture system utilisingtonic inhibition mediated by haGlyRs in response tohippocampal ambient glycine and in the context of ahigh Cl- equilibrium potential, as is the case in TLEhippocampal neurons. We showed that hypoactiveneurons increase their ratio between glutamatergicand GABAergic synapses, reduce their dendrite lengthand finally undergo excitotoxicity. Pharmacologicaldissection of the underlying processes revealedionotropic glutamate and TrkB receptors as criticalmediators between neuronal hypoactivity and theemergence of these TLE-characteristichistopathological signs. Moreover, our results indicatea beneficial role for KCC2, since decreasing the Cl-equilibrium potential by KCC2 expression alsorescued hypoactive hippocampal neurons. Thus, ourdata support a causal relationship between increasedhaGlyR expression and the emergence ofhistopathological TLE-characteristic signs, and theyestablish a pathophysiological role for neuronalhypoactivity in the context of a high Cl- equilibriumpotential.

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COMPLEMENT C1Q IS APROINFLAMMATORY STIMU-LUS, AND MANNOSE-BINDINGLECTIN IS AN ANTI-INFLAM-MATORY STIMULUS, FORMICROGLIAL ACTIVATION

Katrin Färber1, Giselle Cheung1, DanielMitchell2, Russell Wallis3, HelmutKettenmann1

1Cellular Neuroscience, Max-Delbrück-Center forMolecular Medicine, Robert-Rössle-Straße 10, 13125Berlin, Germany, 2Clinical Sciences Research Institute,Warwick Medical School, University of Warwick,Coventry CV2 2DX, 3Department of Infection, Immunityand Inflammation Maurice Shock Building, University ofLeicester, PO Box 138, Leicester LE1 9HN UK

Microglia, the immune resident cells of the centralnervous system, permanently screen brain tissueand respond to any kind of pathology anddamage. This response is strongly correlated withchanges in a broad range of microglial functionslike transformation of cell morphology, enhancedrelease of cytokines, chemokines or nitric oxideand the presentation of antigens. In our study, wehave analysed the effects on microglial propertiesof key components and potential initiators of theclassical and lectin complement cascade, C1q(Complement factor 1q) and MBL (Mannosebinding lectin). We show that C1q, the firstcomponent of the classical complement cascadesystem, can trigger the release of IL6, TNF-alpha,and nitric oxide and the oxidative burst in ratprimary microglial cells similar to the classicalpro-inflammatory stimulation by LPS. By contrast,MBL, the first component of the lectin pathwayof complement failed to trigger these parameters,but attenuated the pro-inflammatory responseparameters of LPS. C1q also triggers anintracellular Ca2+ increase. These findings indicatethat C1q fosters while MBL attenuates microglialactivation.

PROTEASOME ACTIVITY RE-STRICTS LONG-TERM MEMO-RY FORMATION IN HONEYBEES(APIS MELLIFERA)

Johannes Felsenberg & Dorothea Eisenhardt*Free University of Berlin, Institute of Biology,Neurobiology, Königin-Luise-Strasse 28/30, 14195 Berlin,*theodora@neurobiologie.fu-berlin.de

Proteasomes are multi-protein complexes thatare degrading proteins. Their target proteins aretagged with ubiquitin by a ubiquitin ligase beforedegradation, to be recognized by theproteasomes. The ubiquitin-proteasome systemplays a crucial role in a number of neuronalprocesses including axon guidance, synapticdevelopment, synaptic function and synaptic

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plasticity. Moreover, a role of the ubiqitin-proteasomein long-term memory formation has been demonstrated.But these results are contradictory. In the crabChasmagnathus the ubiquitin-proteasome system isnecessary for the formation of long-term memory,whereas activity of the ubiquitin-proteasome system inthe amygdala of rats restricts formation of a long-termmemory in a fear conditioning paradigm. In this studywe examine the role of the ubiquitin-proteasome systemin the honeybee (Apis mellifera), an invertebrate modelsystem for learning and memory. We here examined anappetitive pavlovian learning paradigm, the olfactoryconditioning of the proboscis extension response (PER).We systemically injected two proteasome inhibitors atdifferent time points before and after acquisition andtest their effects on learning and memory formation.We find that only a long-term memory is affected by theapplication of these inhibitors after acquisition, whereasacquisition itself and middle-term memory remainunaffected regardless when the inhibitors were applied.Our results support data from the rat showing that theubiquitin-proteasome system restricts long-term memoryformation. Thus it appears that the ubiquitin-proteasomesystem is important to prevent inadequate long-termmemory formation.

CORTICAL CAPILLARIES POSSESSACTIVE CONTRACTILE ABILITIES INSLICE AND IN VIVO: A TWO-PHOTON STUDY

F. Fernández-Klett1 , N. Offenhauser1 U. Dirnagl1,J. Priller2, U. Lindauer1

1Department of Experimental Neurology, Charité Berlin,Germanym, 2Neuropsychiatry and Laboratory of MolecularPsychiatry, Charité Berlin, Germany

The role of capillaries in the regulation of cerebralblood flow remains largely unexplored— yet pericytes,the second cell type of CNS capillaries besidesendothelial cells, are known possess contractileproperties in vitro in retinal and cerebellar preparations(Peppiatt et al., Nature 443:700-704, 2006). The studyof vasoactivity in brain capillaries in vivo has beenhampered by the difficulty to directly observe them. Wehave used the β-actin-eGFP transgenic mouse inconjunction with two-photon microscopy to overcomethis obstacle. In these mice, the expression of GFP byendothelial cells and pericytes allows the imaging ofdynamic changes of capillary morphology at highresolution. In slices of the sensory cortex, we haveobserved a significant constriction occurring in nearbycapillaries after local application of the thromboxan-A2receptor agonist U46619. The constriction wasconcentration-dependent, and prevented by thethromboxan-A2 receptor antagonist, SQ 29,548.Morphologically, the constriction mostly showed asphincter-like pattern and was located near pericytes. Invivo, capillaries showed localized reductions of capillarydiameters, mimicking the morphological featuresobserved in the slice. Overall, a moderate decrease of

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capillary diameters was noted in vivo, paralleled byreductions of capillary red blood cell velocity andperfusion. Our results suggest that capillaries canact as putative regulators of cortical cerebral bloodflow, which opens new avenues for our understandingof cerebral blood flow regulation in the normal anddiseased brain.Supported by the DFG and the Hermann and LillySchilling Foundation.

HETEROSYNAPTIC PLASTICITYAT THE HIPPOCAMPAL OUTPUT

Pawel Fidzinski1,2, Uwe Heinemann1, JoachimBehr1,2

1 Institute for Neurophysiology, Charité UniversitätsmedizinBerlin, Germany, 2 Department of Psychiatry andPsychotherapy, Charité Universitätsmedizin Berlin, Germany

The direct cortical input (dCI) to the hippocampuscomprises axonal projections from the entorhinalcortex that bypass the dentate gyrus and directlyinnervate CA3, CA1 and the subiculum. This inputhas major importance for memory formation as itprovides positional information to hippocampal placecells (Brun et al., 2008). The subiculum (SUB) isregarded as the principal output area for thehippocampus and was shown to play a critical role inmemory formation, however, mechanisms of synapticplasticity at dCI-SUB synapses remain unknown. Herewe report that both homosynaptic long-termpotentiation (LTP) and long-term depression (LTD) atdCI-SUB synapses affect synaptic strength of theCA1-SUB input and that GABAergic transmissioncontrols the direction of this heterosynaptic plasticity.In acute brain slices of juvenile Wistar rats, EPSPs ofsingle subicular neurons were recorded with sharpmicroelectrodes upon stimulation of dCI/CA1efferents. Standard high- (100 Hz) and low-frequency(1 Hz) protocols were applied to induce LTP andLTD, respectively. High-frequency stimulation of dCI-SUB efferents induced LTP at both dCI and CA1inputs, whereas induction of LTP at CA1-SUB efferentswas input-specific. Blocking GABAergic transmissionwith bicuculline converted the heterosynaptic LTP toLTD. Similarly, low-frequency stimulation of dCI-SUBsynapses induced LTD of the dCI input and aheterosynaptic LTP at CA1-SUB synapses, whichcould be switched to heterosynaptic LTD bybicuculline. No heterosynaptic effects were observedafter induction of LTD at CA1-SUB synapses. In thisstudy we demonstrate for the first time that synapticplasticity can be induced at dCI-SUB synapses. Theheterosynaptic effects suggest that the dCI hasmodulatory influence on the hippocampal output,and that this modulation is mediated by inhibitorynetworks. Further experiments are necessary touncover which receptors are involved in bothhomosynaptic and heterosynaptic plasticity of thedCI-SUB input.

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29 INVESTIGATION OF SIGNALLINGPATHWAYS NECESSARY FORCALEB/NGC- DRIVEN DENDRITICSPINE COMPLEXITY

K. Franke, N. Brandt, R. Nitsch, and S.SchumacherInstitute of Cell Biology and Neurobiology; Center for Anatomy,Charité- Universitätsmedizin Berlin, Charitéplatz 1, D-10117Berlin, Germany

Dendritic spines, specialized actin-based protrusionsemerging from dendritic shafts, are the primary sitesof excitatory synapse formation and are thought tofunction as the basic unit of synaptic integration.Transmembrane proteins are important forconnecting extrinsic cues, which regulate dendriteand spine formation, to intracellular mediators ofcytoskeletal rearrangement. Recently we showed thatthe transmembrane protein CALEB/NGC (ChickenAcidic Leucine-rich EGF-like domain-containing Brainprotein/Neuroglycan C), a neural member of theEGF family, mediates dendritic tree and spinecomplexity but that the signalling pathways in therespective processes differ. We found that theextracellular EGF-like domain of CALEB/NGC isnecessary and sufficient for both, increasing dendriticbranching and stimulating spine formation. However,in contrast to CALEB/NGC-mediated dendriticbranching, CALEB/NGC-induced spine formation isnot dependent on an active phosphatidylinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin(mTOR) signalling pathway. Up to now, investigationsof the proteins known to interact with CALEB/NGChave not shed light on this divergence. For a moredetailed characterization of these signalling pathwayswe performed a yeast-two hybrid screen and identifiedB56ß, a subunit of PP2A, to interact with CALEB/NGC. B56b was found to inhibit dendritic branchingbut did not interfere with the intracellular signallingmechanisms of CALEB/NGC-mediated dendriticspine complexity.Literature:Brandt et al., 2007 EMBO J 26, 2371-2386Brandt et al., 2008 FASEB J, accepted

NEUROVASCULAR COUPLING ANDCEREBRAL METABOLIC RATE OFOXYGEN: EFFECTS OF BRAINHYPOTHERMIA

Martina Füchtemeiera, Nikolas Offenhausera,Christoph Leithnera, Jens Steinbrinka, MatthiasKohl-Bareisb, Ulrich Dirnagla, Ute Lindauera,Georg Royla

aDepartment of Experimental Neurology, CharitéUniversitätsmedizin Berlin, 10098 Berlin, Germany,bUniversity of Applied Sciences Koblenz, RheinAhrCampusRemagen, 53424 Remagen, Germany

Background: Neuronal activation is accompaniedby a local increase in cerebral blood flow (CBF) and

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in cerebral metabolic rate of oxygen (CMRO2). Fromcombined measurements of CBF and hemoglobinconcentration, relative changes in CMRO2 duringfunctional challenges can be calculated. Thequantitative relationship between basal CMRO2 andbrain temperature changes over a range of 10K(Q10) has not yet been determined with this methodand can serve as a validation. Then again, theinfluence of hypothermia on neurovascular couplingis not known. We addressed these issues by studyingthe effects of graded hypothermia in a rat model ofneurovascular coupling in the somatosensory cortex.Methods: Anesthetized Wistar rats underwent surgicalpreparation of a closed cranial window over thesomatosensory cortex. Using Laser Dopplerflowmetry and optical spectroscopy, changes in CBFand in hemoglobin concentration were measuredcontinously. Furthermore, an electroencephalogram(EEG) was simultaneously recorded from themeasurement site. By the application of ice packs,whole-body hypothermia was generated, followedby re-warming.Results: Hypothermia led to a decrease ofspontaneous CBF and CMRO2. The calculated Q10value for CMRO2 was 4.4 (95% Confidence Interval:3.7 – 5.1). Parallel to CBF and CMRO2, the powerof the EEG low-frequency-band decreased.Functional changes of CBF and CMRO2 werereduced during hypothermia as well as the amplitudesof somatosensory evoked potentials.Conclusions: With optical methods, spontaneouschanges in relative CMRO2 can be quantified,revealing a Q10 for CMRO2 that is well in the range ofliterature values. During hypothermia, neurovascularcoupling is preserved. This applies to CBF changesaccompanying spontaneous ongoing activity as wellas CBF changes during functional activation.Supported by DFG and Hermann and Lilly SchillingFoundation.

ROLE OF THE TSH1 GENE IN OL-FACTORY BULB – DEVELOPMENT

Garratt, A.N.; Birchmeier, C.; Rocca, E.Max-Delbrueck-Center for Molecular Medicine, Departmentof Neurosciences, Robert-Roessle-Strasse 10, 13125 Berlin

The early development of the olfactory bulb is stillpoorly understood. We chose to analyse the functionof the Tsh1 gene, which we had shown to beexpressed in cells of the outer granule cell layer ofthe embryonic olfactory bulb. Our aim was todetermine the function of Tsh1, a potential integratorof signaling downstream of cell surface receptors(e.g. Wnt/beta-catenin signaling) and a partner forHox-family transcription factors in olfactory bulbdevelopment. The methods employed were classicalmutagenesis in the mouse, together withimmunohistochemistry, in situ hybridisation andmicroarray analysis. Tsh1 was expressed in an earlyemigrating population of GABA-ergic interneurons,generated in the rostral telencephalon around E11-

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E12. In Tsh1 homozygous null embryos, mutantcells clumped together and failed to distribute radiallywithin the olfactory bulb, a phenotype associatedwith changes in Semaphorin signaling. In addition,the Tsh1 mutant cells failed to activate expression ofGABA-ergic markers such as GAD67 and GABA.Conclusions: Tsh1 is essential for the correct radialmigration and differentiation of a pioneer populationof GABA-ergic granule cell neurons within theolfactory bulb. Tsh1 mutant cells failed to expressSemaphorin 3c and a signaling mediator cypin, whichmay account for the aberrant clumping of mutantcells within the center of the olfactory bulb.

EXPRESSION ANALYSIS OF THEPLASTICITY RELATED GENE-1

Beate Geist, Thorsten Trimbuch, Olaf Ninnemann& Robert NitschCharité - University Hospital Berlin, Center of Anatomy,Institute of Cell- and Neurobiology, Berlin

PRG-1 is a membrane associated protein specificallyexpressed in neurons. It is only expressed during latedevelopmental stages and might be involved in theLPA signal transduction pathway. PRG-1 plays alsoan important role in axonal outgrowth and corticallayer formation. The interesting temporal and spatialexpression pattern of PRG-1 raises the question ofit´s specific regulation. In silico analysis indicates aGC-rich TATA-Box less promoter sequence. Severaltranscription start points of the murine gene weremapped via 5´-RACE. Prior treatment with tobaccoacid pyrophosphatase strongly favoured the detectionof CAPed full length transcripts. In order to analyze invivo expression pattern of PRG-1, we generated amouse model using the BAC (bacterial artificialchromosome) transgenic technology according toN. Heintz (Rockefeller Institute). In this transgenicmouse line the reporter protein EYFP is expressed inthe same way as the endogenous PRG-1, controlledvia in situ hybridisation and immunhistochemicalstainings. The strict neuronal expression of the reportergene in absence of conserved motivs mediating thisexpression pattern, like e.g. REST raises hope toidentify a new regulatory motiv, which must belocalised on the 200 kb sequence of the insertedBAC. Besides expression analysis this reporter-mouse-model allows the analysis of PRG-1 regulation duringdevelopment and in cultured organotypic slicepreparations .

MACROPHAGE/MICROGLIAACTIVATION AND ENGRAFTMENTDURING PERSISTENT BORRELIALCNS INFECTION

Harald Gelderblom1, Diana Londono2, ChotimaBoettcher1, Diego Cadavid2, Josef Priller1

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1Molecular Psychiatry, Department of Psychiatry, Charite-Universitätsmedizin, Humboldt-Univeristät, Berlin, Departmentof Neurology and Neuroscience and Center for EmergingPathogens at UMDNJ-New Jersey Medical School, Newark,NJ 0710

Relapsing fever (RF) is a multisystemic borrelialinfection with frequent neurologic involvementreferred to as neuroborreliosis. RF is characterizedby peaks of spirochetemia, attributable to antibodyselection against variable serotypes. In the absenceof B cells, serotypes cannot be cleared, resulting inpersistent infection. We previously identifieddifferences in spirochetemia and disease severityduring persistent infection of SCID mice with isogenicserotypes 1 (Bt1) or 2 (Bt2) of of the RF spirocheteBorrelia (B.) turicatae. To study the consequences ofpersistent CNS-infection with B. turicatae, B cell (Igh6-/-) and B and T (Rag1-/-) cell-deficient mice wereinoculated with Bt1 or Bt2. Bt1 was more tissuetropic than Bt2, not only for brain but also for heart.Igh6-/- mice developed more severe clinical diseasethan Rag1-/- mice. Bt1-infected brains had widespreadmicrogliosis/brain macrophage activation despitelocalization of spirochetes in the leptomeninges ratherthan the brain parenchyma. Persistent infection didnot result in injury to the brain parenchyma. Usingoligoarray analysis we found that the majority of116 significantly upregulated genes in the brain ofinfected Igh6-/- mice refer to functions of the immuneresponse. 27% are known to be upregulated inactivated macrophages/microglia. CXCL13 was themost upregulated gene in the brain. In the blood,CXCL13 and IL-10 were the most abundantchomokines/cytokines. Pathogen load positivelycorrelated with IL-10 in blood, brain, and heart. IL-10 injected systemically reduced disease,spirochetemia, CXCL13 production as well asmicrogliosis. In the brain, activated microglia werethe main source of IL-10. To investigate the influenceof persistent borrelial infection on engraftment anddifferentiation of migratory myeloid cells in the brain,we presently use transplantation of GFP marked BMcells into SCID and immunocompetent mice. Weobserve widespread intraparenchymal engraftmentof F4/80+/Iba-1+/gfp+ cells, predominantly in theproximity of meningeal inflammation and with severalmorphologically distinct forms of macrophages/microglia. CNS involvement in B cell-deficient micepersistently infected with B. turicatae is characterizedby prominent microgliosis as well as upregulation ofgenes suggesting a vigorous immune responsewithout detectable injury. Systemic and microglialproduction of IL-10 may play a protective role as adownregulator of inflammation and pathogen load.Present studies focus on myeloid cell engraftmentand the origin of IL-10 secreting macrophages/microglia during persistent borrelial CNS-infection.

34 COGNITIVE CONTOL OF GOAL-DIRECTED BEHAVIOR: EVENT-RELATED POTENTIALS ASSO-CIATED WITH SELF-GENERATEDAND EXTERNALLY INDUCEDFAILURE

Antje Gentsch1, Peter Ullsperger2, NorbertKathmann3, Tanja Endrass3, Markus Ullsperger4

1Berlin School of Mind and Brain, Berlin, Germany, 2FederalInstitute for Occupational Safety and Health, Berlin, Germany,3Humboldt University, Berlin, Germany, 4Max Planck Institutefor Neurological Research, Cologne, Germany

Goal-directed behavior requires not only thecontinuous monitoring of failures but also the causalattribution of these failures in order to adjust behaviorappropriately. It has been suggested that the error-related negativity (ERN) following response errorsand the feedback-related negativity (FRN) followingnegative response feedback reflect functionally relatedcomponents of the event-related brain potential (ERP)in performance monitoring. However, the majorityof studies focused only on unfavorable outcomeswhich are associated with self-generated errors inreaction time tasks. The objective of the presentresearch was to examine whether the performancemonitoring system is also activated by externallycaused failure. Participants performed a choicereaction time task in which technical problems withthe response device were simulated leading to falsenegative feedback. As expected, an ERN wasobserved following self-generated errors, and a FRNwas elicited following technical malfunctions. Basedon the assumption of a common neural generatorfor both ERP components, theses findings suggest amore general role of the performance monitoringsystem in signaling the need for adjustment, wheneverthe outcome of an action is worse than intended,independently of whether the failure to achieve anaction goal is due to internal or external factors.

APOLIPOPROTEIN E DEFICIENCYENHANCES TAU HYPERPHOSPHO-RYLATION IN P301L MUTANTHUMAN TAU MICE

F. Glöckner and V. MeskeCentrum für Anatomie, Institut für Integrative Neuroanatomie,Charité, Berlin

Clinical studies suggest a link between Alzheimer´sdisease (AD) and imbalances in cholesterolmetabolism and a further modification by theapolipoprotein E (apoE) genetic polymorphism, arisk factor for AD. But whether that link betweenserum cholesterol and AD is due to an influence ofbrain cholesterol homeostasis is yet not understood.Cerebral cholesterol imbalances may trigger theamyloid toxic cascade or influence tauphosphorylation and tangle formation ratherindependently. ApoE plays an important role in the

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cholesterol homeostasis of neurons. To investigatethe possible link between cholesterol and taupathology under the influence of apoE, we useddouble transgenic mice expressing P301L mutanthuman tau but deficient in apoE (TauAPOE-/-) andP301L tau APOE wild type mice (TauAPOE+/+).These mice express the longest human four-repeattau isoform with the human pathogenic mutationP301L and show age-dependent cytoskeletalchanges which resemble those found in AD brain.Mice were kept on a cholesterol-enriched diet (1%cholesterol) or a control diet. Changes in tauphosphorylation and conformation were mostpronounced in the apoE-deficient mice but seemedto be attenuated by the cholesterol-enriched diet.TauAPOE+/+ mice showed remarkably less AT8-(phosphorylation-dependent tau antibody) and MC1-immunoreactivity (conformation-dependent) than theTauAPOE-/- mice and an opposite diet effect. Totalbrain cholesterol was higher in the TauAPOE-/- mice.On the cholesterol-enriched diet, TauAPOE+/+ miceshowed an increase in total brain cholesterol whilethe apoE-deficient mice had no further increasealthough the serum cholesterol level was furtherincreased by the diet in these animals. There was noclear correlation between total brain cholesterol andtau pathology independent of APOE genotype. TheapoE deficiency seemed to influence the pathologicaltau processing in P301Ltau mutant human tau micemore than the high serum cholesterol levels inducedby diet.

TRPV1, A SYNAPTIC PROTEINChandan Goswami and Tim HuchoMax Planck Institute for Molecular Genetics, Ihnestr. 63-73,14195 Berlin, Germany

Electrophysiological studies demonstrate TRPV1 tobe involved in neuronal signal transmissions. Itslocalization along nociceptor fibres is proven butevidence demonstrating the presence of TRPV1 insynaptic structures is lacking. We now find TRPV1 inDRG neuron derived F11 cells at filopodial tips andcell-cell contact regions. There it co-localizes withpre- and post-synaptic proteins such as bassoon,PSD95, and PSD-Zip45. Additionally, it is present incytoplasmic transport packets, which deliver pre-assembled synaptic structures. We observed them inlife cells to perform characteristic fast saltatorymovements. Also, when expressed in cultured corticalneurons, TRPV1 localizes to spines. Accordingly,spine morphology is strongly altered upon TRPV1activation. In filopodia and neurite like structures ofF-11 cells TRPV1 also co-localizes with synapticvesicular proteins such as clathrin, snapin, andsynapsin. In F11 cells vesicle turnover can bevisualized by uptake of the fluorescent dye FM-464.Vesicle release is strongly induced by activation ofTRPV1 with the endogenous agonist NADA. Weconclude that TRPV1 can act both as pre- as well as

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post-synaptic protein. It is present in cycling vesiclesat active zones. Activation of TRPV1 modulates themorphology as well as the function of synapticstructures.

EFFECTS OF SALICYLATE APPLI-CATION ON THE SPONTANEOUSACTIVITY IN BRAIN SLICES OFTHE MOUSE COCHLEAR NUC-LEUS, MEDIAL GENICULATE BODYAND PRIMARY AUDITORY CORTEX

Romy Götze1; Dietmar Basta, PhD2; Arne Ernst,MD2

1Humboldt-University of Berlin, Institute of Biology, Berlin,Germany, 2Department of Otolaryngology at UKB, Hospital ofthe Free University of Berlin, Berlin, GermanySalicylate is a well - known substance to producereversible tinnitus in animals and humans as well. Ithas been shown that systemic application of salicylatechanges the neuronal spontaneous activity in severalparts of the auditory pathway. The effects observedin central auditory structures in vivo could be basedon the changed afferent cochlear input to the centralauditory system or in addition by a direct effect ofsalicylate onto neurons within the auditory pathway.An immediate influence of local salicylate applicationon spontaneous activity of central auditory neuronshas already been described for the inferior colliculus(IC) in brain slice preparations. As spontaneous activitywithin all key structures of the central auditory pathwaycould play an important role in tinnitus generation,the present study investigated direct effects of salicylatesuperfusion on the spontaneous activity of thedeafferentiated cochlear nucleus (CN), medialgeniculate body (MGB), and auditory cortex (AC) inbrain slices. Out of 72 neurons, 73.4 % respondedstatistically significantly to the superfusate by changingtheir firing rates. 48.4 % of them increased and51.6 % decreased their firing rates, respectively. Themean change of firing rate upon salicylate superfusionwas 24.4 %. All responses were not significantlydifferent between the brain areas. The amount ofneurons which responded to salicylate and the meanchange of firing rate was much higher in the IC thanin the CN, MGB and AC. This contributes to thehypothesis that salicylate-induced tinnitus is a phantomauditory perception mainly related to hyperexcitabilityof IC neurons. However, the present results suggestthat the individual, specific salicylate sensitivity ofCN, MGB and AC neurons can modulate thesalicylate-induced generation of tinnitus.

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38 ACUTE AND LONG-TERM EFFECTSOF NOISE EXPOSURE ON THE AS-CENDING AUDITORY PATHWAYEVALUATED WITH MANGANESE-ENHANCED MAGNETIC RESO-NANCE IMAGING (MEMRI)

Moritz Gröschel1, Susanne Müller3, Romy Götze1,Christian Bauknecht4, Randolf Klingebiel4, ArneErnst2, Dietmar Basta1, 2

1Institute of Biology, Humboldt-University of Berlin, Germany,2Department of ENT at UKB, Free University of Berlin,Germany, 3Neuroscience Research Center, CharitéUniversity Medicine Berlin, Germany, 4Department ofNeurology, Charité University Medicine Berlin, Germany

Noise exposure leads beside cochlear hair cell lossto profound long term changes within the centralauditory pathway. A modified spontaneous activity,changes in cell density and neurotransmitter actionwere reported for several auditory structures. It is notpossible yet to distinguish between the changes basedon the reduced input from the noise-damaged organof corti and neuronal changes directly related to theauditory overstimulation. For the understanding ofnoise induced functional disabilities, it seems to beimportant to clarify the influence of these twomechanisms. While hair cell loss appears slowly inthe early days after treatment, it should be possible tostudy effects on central auditory structures at differentstages after an overstimulation. In this study, normalhearing mice were noise-exposed (3h, 115 dB SPL,white band noise 5-20 kHz) under anaesthesia. Atthe end of the treatment or one week later animalsreceived an i.p. injection of manganese chloride tomonitor neuronal activity by using 7T-MRI scanning(replacement of calcium influx by manganese). Signalintensities of dorsal (DCN) and ventral (VCN)cochlear nucleus, periolivary nucleus (PON), inferiorcolliculus (IC), medial geniculate body (MGB) andprimary auditory cortex (AI) were measured andcompared with controls. The acute group withtemporary hearing loss showed a significant signalenhancement in the DCN and VCN. The animalscharacterized by a permanent hearing loss have asignificantly higher neuronal activity also in higherstructures of the auditory pathway. The resultsdemonstrate that acoustic overstimulation directlyinfluences the neuronal network within the centralauditory pathway. Acute noise exposure seems toaffect the lower auditory pathway, whereas long-termeffects could also be observed in higher structures.

ALTERATIONS IN THE ENTORHNALCORTEX NETWORK OSCILLA-TIONS IN A MOUSE MODEL OFMESIAL TEMPORAL LOBEEPILEPSY

S. Gurgenidze, T. Dugladze, Heinemann and T.GloveliIstitute of Neurophysiology, Charité Universitätsmedizin Berlin

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Mesial temporal lobe epilepsy (mTLE) is the mostcommon form of epilepsy, characterized by recurrentcomplex partial seizures and hippocampal sclerosis.mTLE patients often display shrinkage of the entorhinalcortex (EC), which has been attributed to neuronalloss in medial EC (mEC). Since the EC occupies apivotal position in gating hippocampal input and outputthe dysfunction of this region may contribute toepileptogenesis in humans. To identify the anatomicaland functional changes, we performed field potentailand patch-clamp recordings in the EC in a kainite(KA) model of mTLE 3-4 weeks followingintrahippocampal KA-injection. Field potentialrecordings were done from different region of theEC. Whole-cell patch-clamp recordings in currentand voltage clamp mode were obtained from mEClayer III parvalbumin positive (PV+) interneurons fromcontrol and KA-treated mice. Our results show thatKA-induced field gamma oscillatory activity in the EChas significantly higher power in epileptic than incontrol mice. Morphological analysis of PV+interneurons in layer III of the EC revealed no cleardifferences in the axonal arborisation pattern betweencontrol and experimental groups. As cell loss inlayer III of the EC is restricted to excitatory cells wepresume a stronger interaction between theGABAergic interneurons in mTLE. An alteredinteraction between the GABAergic inhibitoryinterneurons in the EC network may contribute toaltered rhythmogenesis and the development ofseizure activity in mTLE.This study was supported by the FP6 (EPICURE).

FREQUENCY AND PHENOTYPE OFNK CELLS IN MULTIPLE SCLERO-SIS

I. Hamann, M. Paterka T. Prozorovski, KalliopiPitarokoili , F. Zipp and C. Infante-DuarteCecilie Vogt Clinic for Neurology, Charité - UniversityMedicine Berlin, Germany , isabell.hamann@charite.de

Multiple Sclerosis (MS) is considered an autoimmunedisease of the central nervous system of unknownpathogenesis. We previously demonstrated asignificantly lower expression of the chemokinereceptor CX3CR1 on NK cells in relapsing-remitting(RR) MS patients compared to healthy individuals andfound an association between disease activity andfrequency of CX3CR1-positive NK cells in MSpatients. To better elucidate the possible role of NKcells (and in particular CX3CR1-expressing NK cells)during MS pathology, we investigated the frequencyof NK cells in cerebrospinal fluid (CSF) of MSpatients, and the phenotype and effector function ofCX3CR1+ vs. CX3CR1- NK cells. The frequency ofNK cells in the CSF and blood was comparedbetween MS patients and patients with non-inflammatory neurological diseases (NIND). Our datashow the blood/CSF ratio of NK cells is 7:1 in MSpatients and is 2:1 in NIND. The ratio of T cellswas comparable between the two groups of patient.

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Related to the investigation of CX3CR1-expressingNK cells, we demonstrate that humanCX3CR1negative/low- NK cells produceincreased amounts of the cytokines TNF-alpha, GM-CSF, IL-10, IL-13 and IL-5, are more activated (butless cytotoxic), and show increased proliferativecapacity in response to IL-2 when compared with theCX3CR1-positive fraction. Thus, in contrast to theCX3CR1-positive NK cells, the NK cells that are lowor negative for the receptor, present a regulatoryphenotype characterized by a diminished cytotoxicityand a high production of soluble factors. Altogether,our findings highlight the overall importance of NKcells in MS and the necessity to learn more abouttheir role in MS.

DENSITY OF ENKEPHALIN EXPRES-SING STRIATAL PROJECTION NEU-RONS AND ENTOPEDUNCULARDYNORPHIN IMMUNOREACTIVITYARE UNALTERED IN A MODEL OFPAROXYSMAL DYSTONIA

M. Hamann, A. Kreil, A. RichterFreie Universität Berlin, Department of Veterinary Medicine,Institute of Pharmacology and Toxicology, Koserstraße 20,14195 Berlin

The pathophysiology of hereditary dystonia is stillunknown, but it is regarded as a basal ganglia disorder.Recent studies in the dtsz hamster, an animal modelof paroxysmal dystonia, demonstrated a reduceddensity of striatal GABAergic interneurons at an ageof maximum severity of dystonia (30-42 days oflife) in comparison to non-dystonic controls. Thereduced density coincides with a decreased neuronalactivity and an altered neuronal pattern in theentopeduncular nucleus (EPN), a basal ganglia outputstructure, which receives inhibitory input from thestriatum via the so-called direct pathway. In the presentstudy, the density of striatal met-enkephalin (ENK)expressing GABAergic neurons, which project to theglobus pallidus (indirect pathway) and theimmunoreactivity of dynorphin A (DYN), which isexpressed in striatal neurons of the indirect pathway,were determined in dtsz and control hamsters byusing an image analysis system in a blinded fashionto clarify a possible role of an altered ratio betweenstriatal interneurons and projection neurons. Neitherthe density of striatal ENK+ neurons nor theimmunoreactivity of DYN, determined in the EPN,significantly differed between mutant and controlhamsters. Consequently, alterations seem to berestricted to GABAergic interneurons in the dtszmutant. Thus, the present results support the hypothesisthat an altered ratio between striatal interneurons andprojection neurons leads to imbalances in the basalganglia network and results in a reduced neuronalactivity and altered pattern in the EPN.Supported by the DFG (Ri 845).

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42 GAMMA OSCILLATIONS ANDSPONTANEOUS NETWORK ACTI-VITY IN THE HIPPOCAMPUS AREHIGHLY SENSITIVE TODECREASES IN PO2 ANDCONCOMITANT CHANGES INMITOCHONDRIAL REDOX STATE

C. Huchzermeyer, K. Albus, H.-J. Gabriel, J.Otáhal, N. Taubenberger, U. Heinemann, R.Kovács, O. KannInstitute for Neurophysiology, Charité-UniversitätsmedizinBerlin, 10117 Berlin, Germany

Gamma oscillations have been implicated in highercognitive processes and might criticallydepend onproper mitochondrial function. Using electrophy-siology, oxygen sensormicroelectrode and imagingtechniques, we investigated the interactions ofneuronal activity, interstitial pO2 and mitochondrialredox state (NAD(P)H and FAD fluorescence) in theCA3 subfield of organotypic hippocampal slicecultures. We find that gamma oscillations andspontaneous network activity decrease significantlyat pO2 levels that do not affect neuronal populationresponses as elicited by moderate electrical stimuli.Moreover, pO2 and mitochondrial redox states aretightly coupled, and electrical stimuli reveal transientalterations of redox responses when pO2 decreaseswithin the normoxic range. Finally, evoked redoxresponses are distinct in somatic and synapticneuronal compartments and show different sensitivityto changes in pO2. We conclude that the thresholdof interstitial pO2 for robust CA3 network activitiesand required mitochondrial function is clearly abovethe ‘critical’ value, which causes spreading depressiondue to generalized energy failure. Our study highlightsthe importance of a functional understanding ofmitochondria and their implications on activities ofindividual neurons and neuronal networks.Supported by Deutsche ForschungsgemeinschaftGrants SFB-665 (OK) and SFB-507 (OK, UH) andby „Stiftung zur Förderung der Erforschung von Ersatz-und Ergänzungsmethoden zur Einschränkung vonTierversuchen“ (KA)

MOLECULAR INTERACTIONSBETWEEN STOMATIN-LIKEPROTEINS AND ACID-SENSING IONCHANNELS

Julia Jira, Paul HeppenstallCharité CBF, Klinik fuer Anaesthesiologie, Hindenburgdamm30, 12200 BerlinStomatin-like proteins (SLPs) are widely expressedacross species and tissues. However, the function ofthis family of membrane-associated proteins remainsto be elucidated. Some SLPs bind cholesterol as wellas actin filaments and are therefore considered tohave a scaffolding function, assembling proteincomplexes at the plasma membrane. Moreover,

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there is evidence of SLPs directly interacting with ionchannels. In the nematode worm C.elegans, thestomatin homolog MEC-2 plays an essential role inmechanosensation by anchoring the transductionchannel MEC-4 to the cytoskeleton. We are interestedin defining the nature of the interactions betweenmammalian counterparts of the C.Elegans proteins,which have been implicated in mechanotransductionas well. To this end, we have performed co-immunoprecipitation and FRET experiments toexamine interactions between mouse stomatin-likeprotein 3 (mSLP3) and members of the acid-sensingion channel (ASIC) family. These are sodiumchannels that are homologous to the C. elegansMEC-4 channel and comprise short intracellular N-and C-termini, two transmembrane domains and alarge extracellular loop.All ASIC subunits (ASIC1a,1b, 2a, 2b, 3 and 4) and mSLP3 were epitopetagged and transiently transfected into two cell lines(COS-7 and CHO) that are thought to contain noendogenous ASICs. We found that mSLP3 didimmunoprecipitate with all ASICs. Interestingly, a splicevariant of ASIC3, which misses the C-terminus andthe second transmembrane domain, also interactedwith mSLP3. This suggests that the interaction site islocated more towards the N-terminus of the ASICchannels.

CALEB, AN ACTIVITY-REGULATEDPROTEIN, IS INVOLVED IN THEESTABISHMENT OF SYNAPTICCONNECTIONS IN THE CERE-BELLUM

Jüttner, R.1, Craveiro, R.B.1, Montag, D.2, andRathjen, F.G.1

1Max-Delbrueck-Center for Molecular Medicine,Developmental Neurobiology, Berlin, 2Leibniz Institute forNeurobiology, Magdeburg

Proteins, located at the cell surface and modulatedby neuronal activity might be promising candidatesto transform sensory information into a specificsynaptic function including morphological correlates.CALEB, a member of the EGF-family wascharacterized to be activity-dependent processed onthe cell-surface. Developmental regulated expressionpatterns, with peak levels in periods of synaptogenesisand synapse refinement makes CALEB a promisingcandidate to be involved in regulation synapticconnectivity. Analysis of synaptic connectivity in theimmature colliculus superior revealed that CALEBregulates the release probability of theneurotransmitter, while the number and morphologicalcharacteristics of synapses remained unchanged theabsence of CALEB. In the immature cerebellum CALEBis expressed within in the Purkinje cell layer, whilelater in development it is primarily found in themolecular layer. The developmental change in thelocalization in a period of synapse elimination maysuggest a specific function in synapse refinement.

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Analysis of the climbing fiber - Purkinje cell synapserevealed an earlier maturation of the adult-like,monosynaptic innervation in the CALEB knockoutmouse compared to the wild type. This faster synapseelimination appears not to be induced by mGluR-mediated signalling of parallel fibers. However, theGABAergic input to Purkinje cells seems to bereduced, represented by reduced amplitudes ofspontaneous inhibitory postsynaptic currents. Thesechanges in the maturation of synaptic connectivity inthe cerebellum lead, at least, to deficiencies in themotor coordination of the knockout mouse. Insummary, CALEB is an activity-dependent regulatedprotein, which plays a role in adjustment of neuronalnetworks.

EARLY MATURATION OFGABAERGIC SYNAPSES IN MOUSERETINAL GANGLION CELLS

Jüttner, R., Unsoeld, T., Stradomska, A.M.,Wang, R. and Rathjen, F.G.Max-Delbrueck-Center for Molecular Medicine,Developmental Neurobiology, Berlin, GermanyThe formation of complex neuronal circuits iscoordinated by numerous molecular and cellularmechanisms. To unravel the specific function ofproteins that participate in the establishment andmodulation of synaptic connections, investigationof transgenic mice remains a promising approach.In order to capitalize fully on these experimentaladvantages, it is important to establish developmentaltimelines of the major functional parameters. Thisstudy was aimed to characterize the earliest phasesof synapse development in mouse retinal ganglioncells (RGCs) by recording spontaneous postsynapticcurrents (PSCs). RGCs were identified on the basisof their location in the ganglion cell layer, their somasize and the presence of voltage-activated Na+currents. First postsynaptic currents were detected atembryonic day 17 with a success rate of about 54.5% (6/11), while later in development (P6) nearly allRGCs showed synaptic events (96.6 %, 28/29). Inthe presence of bicuculline, a GABAA receptorblocker, all synaptic currents were completelysuppressed, suggesting their GABAergic nature. Inthe first postnatal week only in three RGCs out of135 (2.22 %) spontaneous, fast decaying eventscould be detected, representing most likelyglutamatergic currents. By analysing GABA-inducedCa2+ transients we show, that GABA-mediatedsignalling acts in an excitatory manner in this period.The present results suggest that functional GABAergicsynapses with RGCs appear before birth and thatGABAergic synaptic transmission precedes that ofglutamate in the retina. In this early period GABAacts in a depolarizing manner and takes over anexcitatory function.Supported by GRK 268 at the Humboldt University(Berlin).

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46 LYSOPHOSPHATIDIC ACID INSYNAPSOGENESIS

Kieselmann O1, Grantyn R2, Singh B2, Aoki J3,Nitsch R1, Bräuer AU1.1. PRG Research Group, Institute for Cell Biology andNeurobiology, Center for Anatomy, Charité –Universitätsmedizin Berlin, Germany; 2. Johannes-Müller-Centrum für Physiologie Berlin, Germany, 3. Graduate Schoolof Pharmaceutical Sciences, The University of Tokyo, Japan

Lysophosphatidic acid (LPA) is a small phospholipidwith a variety of biological actions. This mediatorproduces diverse cellular and biochemical responsesin a range of different nervous system-derived cells.LPA mediates effects through cell-surface receptors(LPA-1-5), following the intracellular activation ofmultiple G-proteins. Our real-time PCR analysis ofmRNA from hippocampal primary neurons onlydetected LPA-1, LPA-2 and LPA-4 receptors, wherebyLPA-2 receptors exhibited the highest expression. Thesame results were found in vivo. In further experimentswe focused on the LPA-2 receptor and analyzed itssubcellular localization in hippocampal primaryneurons. We located the receptor in the cell bodyand dendrites. Interestingly, it was colocalized withdifferent pre-synaptic markers and was present inglutamatergic but not in gabaergic neurons. Infunctional analyses we tested LPA-effects on primaryneurons. We discovered a reduction of synaptophysin-positive terminals and a calcium increase after LPAapplication. LPA-Signaling is controlled in vivo bylipid phosphate phosphatases (LPPs), ectoenzymesthat regulate LPA-levels through dephosphorylation.In our previous studies we identified a set of proteinsthat form a novel subclass in the LPP-superfamily,plasticity-related genes (PRGs). Currently we arefocusing on PRG-1 alone. Unlike other members ofthe LPP-family, PRG-1 is specifically expressed in thebrain and neurons; presynaptic colocalization hasnot yet been identified. Immunohistochemistry showedthe localization of PRG-1 in filopodia and dendriticspines. Furthermore, an overexpression of PRG-1was able to attenuate LPA effects in glutamatergicneurons.

DRUG TRANSPORTERS IN HUMANEPILEPTIC BRAIN – FUNCTIONALSTUDIES

S. Kim1, N. Sandow1, R. Kovacs1, C. Raue1, D.Päsler1, P. Fidzinski1, M. Alam1+, Z.-J. Klaft1, L.Leite Antonio2, U. Heinemann1, S. Gabriel1, andT.-N. Lehmann1*1Institute of Neurophysiology, 1*Department of Neurosurgeryand 1+Department of Neurology, Charité-University MedicineBerlin, Berlin, Germany; 2Neurologia Experimental,Universidade Federal de Sao Paulo-Escola Paulista deMedicina, Sao Paulo, Brazil

Ectopic expression of multidrug transporter proteins(Pgp, MRP1, MRP2) in astrocytes or neurons hasbeen observed in resected tissue of patients suffering

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from pharmacoresistant mesial temporal lobeepilepsy. There are also case reports where theapplication of inhibitors of multidrug transportersimproved the outcome of patients. Here we inducedpharmacoresistant activity (carbamazepine 50µM orvalproate 1mM) in human hippocampal(Hi) andcortical(Co) slices in vitro and we investigated theeffect of inhibitors of multidrug transporter proteinsby application of probenecid (400µM) and verapamil(40µM). The type of epileptiform activity was rarelyaffected in the hippocampus (76% stable, 8%replaced by interictal activity, 16% suppressed), incontrast to the cortex (43% stable, 38% replaced,19% suppressed). The quantitative analysis revealedsignificant reductions for the combined treatment inslow field potential shift(Hi, Co), maximumamplitude(Hi, Co), frequency of superimposedoscillations(Hi) and duration(Co) of the events.Preliminary analysis of our control experimentsshowed that a longer incubation time of both inhibitorsis more effective in the hippocampus, but not in thecortex. But in the cortex, the inhibitors given aloneshowed more effect than the application of a singleantiepileptic drug. The electrophysiological effectsof the inhibitors could not be correlated to theexpression rate of multidrug transporter proteins inthe hippocampus.Supported by a grant of the DFG SFB T3 to TNL andUH and by CAPES Brazil to LLA

DEVELOPMENTAL DOWN-REGU-LATION OF EXCITATORY GABA-ERGIC TRANSMISSION IN NEO-CORTICAL LAYER I VIA PRE-SYNAPTIC ADENOSINE A1RECEPTORS

S.Kirischuk, R.Grantyn, A.Dvorzhak, K.KirmseInstitut für Neurophysiolgie, Charité-Universität-MedizinBerlin,Tucholskystr. 2, 10117 Berlin

Layer I of the developing cortex contains a denseGABAergic fiber plexus. These fibers provideexcitatory inputs to Cajal-Retzius (CR) cells, the early-born neurons in layer I. CR cells possess an extensiveaxonal projection and form synaptic contacts withexcitatory neurons. Interestingly, activity of CR cellsdeclines during the first postnatal week. Here werecorded IPSCs in CR cells at postnatal day (P) 1-2and P5-7. Blockade of adenosine A1 receptors(A1Rs) increased the amplitude of evoked IPSCs(eIPSCs) and decreased paired-pulse ratio at P5-7but not at P1-2. A1R activation decreased the meaneIPSC amplitude at P5-7, but failed to affect eIPSCsat P1-2. Ecto-ATPase inhibition completely abolishedthe A1R-mediated effects suggesting that extracellularATP is the main source of adenosine. Because A1Rblockade did not affect the median mIPSC amplitude,our results demonstrate that adenosine reducesGABA release probability via presynaptic A1Rs atP5-7. As neuronal activity in layer I can depolarize

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pyramidal neurons influencing thereby glutamatergicsynaptogenesis in the lower cortical layers, postnatalweakening of GABAergic transmission byadenosinergic system might reflect a developmentaldown-regulation of this excitatory drive whenglutamatergic synapses are formed.

ACTIVITY OF THE GABA TRANS-PORTER 1 REGULATES GABA-ERGIC SYNAPTIC TRANSMISSIONIN STRIATAL PROJECTIONNEURONS

Knut Kirmse, Rosemarie GrantynDevelopmental Physiology Labs, Institute for Neurophysiology,University Medicine Berlin (Charité), Germany

In the present whole-cell patch clamp study we haveaddressed the possibility that a GABA transporter(GAT-1 or -3) shapes GABAergic synaptictransmission in acute slices of the mouse neostriatum.We have used the degree of GABA(B) receptoractivation as a reporting tool to identify alterations ofperisynaptic GABA concentration. It was found thatpresynaptic GABA(B) receptors are functional andinhibit the synaptic release of GABA, and there wasno indication of a tonic GABA(B) receptor actionunder standard conditions. However, treatment withthe specific GAT-1 blocker NO-711 resulted in loweramplitudes of evoked IPSCs (eIPSCs), prolongedeIPSC decay and higher paired-pulse ratio (PPR).Subsequent application of CGP55845 (a specificGABA(B)R antagonist) partly restored the eIPSCamplitude and reduced the PPR to control levels. Theamplitude of miniature IPSCs decreased after NO-711 treatment independently of GABA(B)R activation.The GAT-3 blocker SNAP-5114 had no significanteffect on the eIPSCs, but a contribution of GAT-3was unmasked by NO-711 suggesting that GAT-1can compensate for a loss in GAT-3 activity. Weconclude that, by mediating the clearance ofperisynaptic GABA, GAT-1 controls the degree ofpresynaptic GABA(B) receptor activation and,therefore, the strength of GABA release. The efficacyof GABA clearance may also affect the GABA(A)receptor-mediated postsynaptic response. Thus, GAT-1 activity should be considered as a factor in the pre-and postsynaptic regulation of GABAergic synaptictransmission in output neurons of the murine striatum.Supported by a grant of the DeutscheForschungsgemeinschaft to RG.

METABOLIC CONSEQUENCES OFSTORE OPERATED CAPACITATIVECA2+ ENTRY

R. Kovács, N. R. Taubenberger, C.Huchzermeyer, U. Heinemann, O. KannInstitute for Neurophysiology, Charité-UniversitätsmedizinBerlin, Germany

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Metabotropic receptor-mediated Ca2+ signals arecritical for the crosstalk of neuronal activity andmitochondrial functions. However, very little is knownabout the effects of store operated capacitative Ca2+

entry on the regulation of energy metabolism inneurones. Here we investigated the effects ofmuscarinic metabotropic receptor activation andsubsequent capacitative Ca2+ entry on mitochondrialCa2+ concentration ([Ca2+]m), mitochondrialmembrane potential and oxidative metabolism(NAD(P)H and FAD fluorescence) in hippocampalslice cultures by using electrophysiology (patch clamprecordings and ion sensitive electrodes) andconventional or 2-photon laser scanning confocalmicroscopy. Application of carbachol (100 µM)transiently increased [Ca2+]m, stimulated oxidativemetabolism and induced K+ outward currents.Carbachol-induced responses persisted in Ca2+ freesolution and blockade of ionotropic glutamatergicand nicotinic receptors as well as voltage-gated Na+

channels. After carbachol induced depletion ofintracellular Ca2+ stores in Ca2+-free solution, re-application of 1.6 mM Ca2+-containing solutiontriggered mitochondrial depolarisation, markedelevations in neuronal [Ca2+]m, and extracellular K+

concentration as well as changes in oxidativemetabolism. The metabolic response upon re-application of Ca2+ required simultaneous activationof muscarinic receptors as it could be blocked bysubsequent application of atropine. By varying theinterval between store depletion and Ca2+ re-application we determined the time course of thecarbachol dependent sensitization of mitochondrialmetabolism and [K+]o transients, which was inagreement with the decay time of the carbacholinduced membrane depolarisation in pyramidal cells.Thus we concluded that store-operated capacitativeCa2+ entry might regulate energy metabolism inconcert with a muscarinic receptor dependent Ca2+-activated K+ current.Supported by the Deutsche Forschungsgemeinschaft(SFB 507) to UH and OK.

ESTROGEN INDUCES TRPV1-DEPENDENT CYTOSKELETALREARRANGEMENT

Julia Kuhn, Chandan Goswami, Tim HuchoMax Planck Institute for Molecular Genetics, Ihnestr. 63-73,14195 Berlin, Germany

The non-selective cation channel TRPV1, thecytoskeleton, and the steroid hormone estrogen areknown to be involved in nociception. However, littleis known if these components are functionally linked.Here we show estrogen to induce rapid morphologicalchanges such as cell retraction, lamellipodia tofilopodia transition, varicosity formation and growthcone retraction in DRG-neuron derived F-11 cellsexpressing TRPV1. The morphological changes inresponse to estrogen correlate with rapid

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rearrangement of the actin network and quickdisassembly of dynamic peripheral microtubules inlife cells. These effects are dependent on theexpression of TRPV1 but cannot be blocked by 5'-I-RTX. 5'-I-RTX is a specific inhibitor of TRPV1 channelopening, thus indicating a channel independent roleof TRPV1 in estrogen-induced cytoskeletonrearrangement. Estrogen can act through the classicalestrogen receptors, ER-α and ER-ß, as well throughthe recently identified G-protein coupled receptorGPR30. The estrogen derivates G-1 and ICI182,780are reported to activate specifically GPR30 while notbeing agonists of the classical estrogen receptors.Estrogen apparently acts through GPR30 on thecytoskeleton as G-1 and ICI182,780 induce similarmorphological changes. We conclude that estrogencan act via the novel estrogen receptor GPR30 onTRPV1 expressing neuronal cells by inducingrearrangements of the actin and tubulin cytoskeleton.

SEQUENTIAL MATURATION OFSENSORY NEURON MECHANO-TRANSDUCTION DURING EMBRY-ONIC DEVELOPMENT

Stefan G. Lechner, Rui Wang, Henning Frenzel,Gary R. LewinMax Delbrück Centrum für Molekulare Medizin (MDC)Berlin-Buch, Neurowisssenschaften, Robert Rössle Str. 10,13125 Berlin

We and others have previously reported the presenceof three types of mechanically activated currents inadult mouse dorsal root ganglion (DRG) neurons.These currents can readily be distinguished by theirinactivation kinetics and are thus classified into rapidlyadapting (RA-type), intermediately adapting (IA-type)and slowly adapting (SA-type) currents. In the presentstudy we asked when during embryonic developmentsensory neurons acquire these mechanosensitivecurrents. Our data suggests that mechanosensitivecurrents emerge in three major waves, which coincidewith already well-described epochs in the developmentof the sensory ganglia. First, at E13.5, mechano-receptors and proprioceptors acquire RA-typecurrents, followed by nociceptors which start toacquire RA-currents at E15.5. The third wave ofmechanosensitivity occurs just after birth when a largeproportion of nociceptors acquire SA-type currents.In addition we investigated the electrical properties ofdeveloping sensory neurons. We found that both,mechanoreceptors and nociceptors, becomeelectrically excitable immediately after they are born,at E11.5 and at E12.5-E13.5, respectively. Thus theacquisition of electrical excitability precedes that ofmechanosensitivity by approximately two days.Moreover, we found that the emergence ofmechanically gated currents in nociceptors correlateswith significant changes in the electrical excitability ofthese neurons. Since the first two waves coincidewith the innervation of peripheral targets by mechano-

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receptors (E13.5) and nociceptors (E15.5), we nextasked whether target derived factors are required forthe acquisition of mechanosensitivity. Therefore DRGneurons from non-mechanosensitive stages weredifferentiated in-vitro in the presence of differentneurotrophins. These experiments strongly suggestthat the acquisition of mechanosensitive currents bynociceptors is induced by target derived NGF, whereasthe acquisition of RA-currents by mechanoreceptorsseems to be a time dependent process which isindependent of the presence of neurotrophic factors.Supported by SFB 665

DOES AGING INFLUENCE PHYSIO-LOGICAL NEUROVASCULARCOUPLING? A COMBINED DC-AGNETOENCEPHALOGRAPHICAND TIME-RESOLVED NEAR-INFRARED SPECTROSCOPICSTUDY

S. Leistner1, T.H. Sander2, H. Wabnitz2, M.Burghoff2, G. Curio1, R. Macdonald2, L. Trahms2,B.-M. Mackert1,3

1 Dept. of Neurology, Charité, CBF, 2 Physikalisch-Technische Bundesanstalt, 3 Dept. of Neurology, VivantesAuguste Viktoria Klinikum; BerlinDifferent fMRI studies have demonstrated that BOLDsignal changes are determined by severalphysiological parameters, such as age. Onehypothesis is that age-dependent changes of thecerebral vasculature influence the neuro-vascularcoupling, leading to attenuated BOLD responses inspite of similar neuronal activation. To characterizeage related dynamics and the interrelation of neuronaland vascular responses, simultaneous unmodulatedDC-Magnetoencephalography (DC-MEG, BMSR-2)and time-resolved multichannel near-infraredspectroscopy (trNIRS) were performed in two agecohorts during motor cortex activation. 10 subjectsaged 20-25 years compared to 10 subjects aged70-75 years performed prolonged finger movementperiods of the right hand (alternating 30 sec.movement/ 30 sec. rest; n=30). DC-MEG and tr-NIRS were recorded over the left motor cortex. Inextension to recent modulation-based MEGrecordings, unmodulated DC-MEG allows tocharacterise neurovascular physiology not only inthe low frequency range but also simultaneously upto the millisecond range, which is important inparticular at the beginning and end of activation. Thepresent study demonstrated the feasibility of combinedrecordings in both age cohorts. Ongoing data analysisalready demonstrated a rapid MEG onset and a muchslower decay at the end of the movement periodwhich can now be described in the relation to theNIRS signal on a scale of tenth of ms. Further groupdata analysis will show if there are significant ageflow change leading to widespread cortical infarcts.It represents an inverse hemodynamic response to

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related neurovascular coupling differences betweenboth groups. This dual measuring technique providesa new non-invasive recording tool to prove alsopathophysiological cerebral coupling concepts, e.g.,in stroke, hypertension and Alzheimer’s disease.

MOLECULAR MECHANISMSUNDERLYING AMYLOID BETAMODULATING EFFECTS OFFENOFIBRATE AND CELEBREX

Lill, C.M.1,2, Thomas A. V.1, Herl L.1, Deng A.1,Hyman B.T.1, Berezovska O.1

1MassGeneral Institute for Neurodegenerative Disease,Massachusetts General Hospital and Harvard MedicalSchool, Boston, 2Cecilie Vogt Clinic for Neurology, Charité–Universitaetsmedizin, BerlinAmyloid ß (Aß) protein is produced by cleavage ofthe amyloid precursor protein (APP) by the beta-siteamyloid precursor protein cleaving enzyme (BACE)and Presenilin (PS) 1 as the catalytic site of the gamma-secretase. Production of Aß as species of differentlength, mainly Aß40 and the highly fibrillogenic Aß42,depends on the precision of the PS1 cleavage site.ur previous data suggest that familial Alzheimer’sdisease (FAD) PS1 mutations increasing the Aß42/40 ratio cause a consistent alteration in PS1conformation and that Aß42-lowering NSAIDs leadto inverse conformational changes. Several othercompounds, e.g. fenofibrate and celebrex, haverecently been reported to increase Aß42/40 ratio,the exact mechanism remains however unclear. Theaim of this study is to determine if the increase inAß42/40 ratio due to fenofibrate and celebrextreatment correlates with change in PS1conformation, PS1/APP alignment, and/orsubcellular distribution of the APP-PS1 complex. Weused an established Fluorescent Lifetime ImagingMicroscopy (FLIM) assay to monitor PS1conformation and alignment of APP with PS1 inintact cells. Furthermore, we applied a novel FRETprobe GFP-PS1-RFP fusion protein to monitor PS1conformation in live cells. Biochemical approacheswere used to investigate APP trafficking andprocessing. We found that fenofibrate and celebrextreatment significantly change PS1 conformationsimilarly to FAD PS1 mutations, and alter thealignment of APP with PS1. Using the GFP-PS1-RFPfusion protein we show that fenofibrate treatmentsignificantly change PS1 conformation in live cells.Furthermore, fenofibrate treatment caused profoundredistribution of APP within the cell. APP maturationwas inhibited resulting in a decreased amount of APPon the cell surface, and full-length (FL) APP wastargeted to the lysosomes. We conclude that a) theAß42-raising effect of fenofibrate and celebrexcorrelates with the change in PS1 conformation andaltered alignment of APP with PS1 similar to that ofFAD PS1 mutations, and b) fenofibrate affects APPmaturation and trafficking.

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55 OLIGODENDROCYTIC COUPLINGIN THE CNS WHITE MATTERRELATED TO CX47 EXPRESSION

M. Maglione*, O. Tress**, K. Willecke**, H.Kettenmann**Max-Delbrück-Center for Molecular Medicine, CellularNeuroscience, ** Institut für Genetik, Universität BonnConnexins, the molecular components of gap-junctions, form connections between cells for cellularcommunication and thereby determine cellularproperties. In the brain, Cx47 as well as Cx32 andCx29 are expressed only in oligodendrocytes, themyelinating cells of the CNS. Several genetic diseasesdemonstrate that Cx32 and Cx47 are fundamentalfor the normal functionality of CNS and PNS myelin.Based on immunocytochemistry and recombinantstudies, oligodendrocytes are not coupled amongeach other, but to astrocytes (Orthmann-Murphy etal., 2008, J Mol Neurosci.). To test for functionalgap-junction coupling, we used the patch-clamptechnique to inject gap-junction permeable dye.Oligodendrocytes were identified by theircharacteristic membrane current pattern and by theirdistinct morphology after dye injection. Injection ofbiocytin into a single oligodendrocyte in acute murineslices of corpus callosum (P10-15) via dialysis withthe patch-pipette led to dye transfer to neighbouringcells in 94% of experiments (N=17). The dye spreadin average to 43 cells. In Cx47 knock-out mice,biocytin spread to an average of four other cells in73% of experiments (N=15). These data suggestthat Cx47-deficiency did significantly affect the sizeof the network of coupled cells, but coupling is stillpresent. To identify the cells coupled in the networkwe developed a method to combine biocytin labelingwith CNPase and GFAP staining, markers foroligodendrocytes and astrocytes, respectively. In thecorpus callosum of wildtype mice (P10-15), mostbiocytin labeled cells were CNPase positive (N=7).The CNPase-negative cells were not astrocytes sincenone of the biocytin-labelled cells were GFAP positive.These results indicate that oligodendrocytes in thecorpus callosum are coupled among each other,but not to astrocytes.

DURATION OF CORTICAL SPREA-DING ISCHEMIA DEPENDS ONINTRACELLULAR CA2+-STORES.

S. Major and J.P. DreierDept. of Neurology and Experimental Neurology, Charité –Universitätsmedizin Berlin, Germany

Delayed ischemic neurological deficit (DIND) is oneof the major complications after subarachnoidhemorrhage (SAH). It occurs in up to 40% of patientswho survive the initial bleeding. About 13% developdelayed cerebral infarcts on CT. Based onexperiments in rats, cortical spreading ischemia (CSI)has been proposed as a mechanism of DIND. CSI isa long-lasting, spreading wave of an ischemic blood

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cortical spreading depolarization (CSD). In SAHpatients CSD occur frequently and correlate positivelywith development of new infarcts if significantlyprolonged (Dreier et al., Brain (2006), 129, 3224–3237). In rats CSI occurs when the Na+ K+ ATPase(NaK) activity and the NO concentration (e.g. due tonitric oxide synthase inhibition by L-NNA respectively)are simultaneously reduced in the subarachnoidspace. Isolated inhibition of Alpha2 and Alpha3isoforms of NaK is sufficient to induce CSI. It leadsindirectly to increase of the cytoplasmic Ca2+

concentration and subsequently to filling of the Ca2+-stores in the sarco/endoplasmic reticulum via theappropriate Ca2+-ATPase (SERCA). Thus we tested, ifdepletion of these internal stores has an influenceon the CSI. A closed cranial window was implantedin rats. Cerebral cortex was superfused with artificialcerebrospinal fluid (ACSF) containing L-NNA (1 mM).Subsequently, thapsigargin (TG), an inhibitor of theSERCA was added to the ACSF at concentration of100 µM. Finally ouabain at 50 µM was applied. TheCBF changes were monitored by Laser-Doppler-Flowmetry. During CSI CBF fell to about 50% ofbaseline value. TG did not prohibit hypoperfusion,but shortened it significantly to 1:16 (0:58 – 3:18)min (vehicle control 4:31(2:07 – 8:47)).

CHARACTERIZATION OF THEPERIPHERAL OSMORECEPTOR

Soeren Markworth, Silke Frahm, Ines Ibanez-Tallon, Jens Jordan* and Gary R. LewinMolecular Physiology of Somatic Sensation, Department ofNeuroscience, Max-Delbrück Center for Molecular Medicine,Robert-Rössle Str. 10, Berlin-Buch, *Franz-Volhard Centrumfür Klinische Forschung, Haus 129, Charité Campus Buch,Wiltbergstr. 50, Berlin-Buch

Peripheral osmosensitive-fibers are believed to belocated in the liver and/or the hepatic branch of theportal vein and project to the CNS via hepatic nerves.They have not yet been visualized or functionallycharacterized, indeed the location and sensory originof such fibers is not known. We show that in rats andmice drinking water leads to a decrease of bloodosmolality in the portal vein by 25mOsm. Wevisualized activation of hepatic sensory fibers byimmunostaining for phosphorylated ERK (extra-cellular-signal-related-kinase). The osmotic stimulusled to a robust induction of pERK in a sub-populationof Isolectin B4-negative sensory nerve fibers. Wemade acute cultures of dorsal root ganglion neuronsfrom the thoracic ganglia (T7-T13) a proportion ofwhich innervate visceral tissues including the liver. Ofthese cells 31% show a robust increase in intracellularcalcium following stimulation with hypotonic solutions(Fura-2 based calcium imaging). Sensory neuronstaken from ganglia that do not innervate viscera hada significantly smaller number of osmosensitive cells.The Transient Receptor Potential Vanniloid 4 (Trpv4)

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is believed to play a role in osmosensation. Here weshow using Ca-Imaging and patch clamp techniquesa significant decrease in osmosensitive cells of Trpv4-/- animals compared to WT only in the thoracic, butnot in the cervical and lumbar region. We alsoexamined a transgenic mouse in which the alpha-3subunit of the nicotinic acetylcholinreceptor is fusedto GFP (green fluorescent protein). We show, thatERK becomes activated in this subpopulation ofGFP+ fibers in the liver after water intake. Thepercentage of GFP+ cells showing osmosensitivityin ca-imaging experiments was much higher thanGFP- cells in thoracic ganglia. This animal model tostudy the activation of peripheral osmoreceptors mayprove a valuable tool to dissect the physiologicalrelevance of this sensory pathway.

THE POTASSIUM THRESHOLD FORCORTICAL SPREADING DEPRES-SION IS INFLUENCED BY AGE ANDEPILEPTIC CHANGES IN RAT ANDHUMAN NEOCORTEX

A. Maslarova, M. Alam, JP. DreierExperimental Neurology, Charité University Medicine, Berlin,Germany

Cortical spreading depolarization (CSD) is a wave ofdepolarization of neurons and glial cells, which ischaracterized by massive ion changes of the intra-and extracellular space and leads to suppression ofneuronal activity. CSD is assumed to be theneurophysiological correlate of the migraine auraand occurs in ischemic stroke, subarachnoidhemorrhage and traumatic brain injury in all investigatedvertebrates including humans. There is evidence thatCSD contributes to neurodegeneration in tissue atrisk and, thereby, to poor clinical outcome. CSDcan be elicited by electric stimulation, chemicalpoisons or Na,K-ATP-ase blockade. Elevatedextracellular potassium level such as in cerebral focalischemia or after brain hemorrhage is another potentinducer of CSD. It was demonstrated before thatchronically epileptic rats are more resistant to CSDinduction than non-epileptic rats. Furthermore, it hasbeen speculated that the human brain shows a higherresistance to CSD compared to rodents. Wecompared the K+ threshold for CSD in human andrat temporal neocortex. Human neocortical sliceswere obtained from surgery on chronically epilepticpatients and compared to chronically epileptic agedrats as well as both young and aged control rats inorder to estimate the impact of age and epilepsy onthe lower susceptibility to CSD. The young controlrats had the lowest threshold, followed by the agedcontrol rats. The highest threshold was observed inepileptic rats and human tissue that did not differfrom each other. Our results imply that both age andchronic epileptic changes in the neocortex decrease

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the susceptibility to CSD under elevated potassiumlevels whereas no significant difference between thespecies was detected.

GABAB RECEPTOR MEDIATEDINHIBITION IN MESIAL TEMPORALLOBE EPILEPSY

N. Maziashvili, T. Dugladze, U. Heinemann,Gloveli T.Institute of Neurophysiology, Charité-UniversitätsmedizinBerlinMesial temporal lobe epilepsy (mTLE) is associatedwith an alteration in the balance of inhibition andexcitation in the hippocampal network. GABA is themajor inhibitory neurotransmitter in the brain, whereit activates both ionotropic GABAA and matabotropicGABAB receptors (GABABR). The alterations in theexpression or function of GABABR have been reportedin human epileptic patients. To identify changes inGABABR mediated transmission in mTLE we

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performed experiments on chronic epileptic micefollowing a unilateral injection of kainic acid (KA)into the dorsal hippocampus. Transverse slices wereobtained from ventral hippocampus of control andKA-injected mice. Extracellular and intracellularrecordings were obtained from area CA3 of thehippocampus. Inactivation of hippocampal GABABRwith CGP55845A (1 µM) in chronic epileptic micedecreased the power of gamma frequency oscillationwhereas it was unchanged in control mice. GABABRagonist baclofen (5-10 µM) completely blocked KA-induced oscillations in control slices and causedtransition from enhanced gamma frequencyoscillations into the pathological activity in slices fromepileptic animals. Intracellular recordings revealedopposite effects of baclofen on the firing propertiesof pyramidal cells: decreases in control and increasesin epileptic mice. These effects were coinciding withthe corresponding changes in the power of thegamma activity. Our results suggest that GABABRmediated inhibition contributes to altered networkoscillatory activity in a mice model of mTLE.This study was supported by the SFB TR3/B5

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PPPPPoster Poster Poster Poster Poster Presentations - Session IIresentations - Session IIresentations - Session IIresentations - Session IIresentations - Session II

HEXOKINASE II - A GLUCOSEDEPENDENT MEDIATOR OFSURVIVAL

Mergenthaler, P.; Freyer, D.; Neeb, L.; Megow,D., Harms, C.; Priller, J.; Dirnagl, U.; and Meisel,A.Experimentelle Neurologie, Charité UniversitätsmedizinBerlin, 10117 Berlin, philipp.mergenthaler@charite.de

Hexokinase II is one of the hexokinase isoenzymesfacilitating the first step of glucose metabolism byphosphorylating glucose. Hexokinases have alsobeen implicated in regulation of apoptosis. Inparticular, mitochondrial binding of hexokinases hasbeen found to show apoptosis modifying features.This association is stabilized by Akt-kinase.Hexokinase II is located in the outer mitochondrialmembrane. This localization may function as a linkof metabolism and apoptosis. We found upregulationof Hexokinase II mRNA as a response to ischemicpreconditioning in cultured rat cortical neurons. Toinvestigate whether this response promotes survival,we studied protective features of hexokinase II in anin vitro model of cerebral ischemia. Employing anovel electroporation approach, hexokinase II wastransfected in embryonic rat cortical neurons. Cultures

60 were submitted to oxygen-glucose-deprivation (OGD),oxygen deprivation (OD) and glucose deprivation(GD), respectively. Compared to controls,Hexokinase II protected transfected neurons fromdamage in OGD and OD experiments but showeddetrimental effects on neurons in GD experiments.We present clear evidence for glucose-dependentsurvival mediated by hexokinase II.

ROLE OF DIFFERENT CTL-EFFEC-TOR MOLECULES IN DAMAGINGTHE NEURO-AXONAL UNIT IN VIVO

D. Merkler1, A. Bergthaler2,3, M. Schedensack1, E.Horvath2, M. Kerschensteiner4, T. Misgeld5, W.Brück1, D. Pinschewer2,3

1Department of Neuropathology, Georg-August-University,Göttingen, Germany, 2Institute of Experimental Immunology,University of Zurich, Switzerland, 3Department of Pathologyand Immunology, University of Geneva, Switzerland, 4Institutefor Clinical Neuroimmunology Research Unit TherapyDevelopment, Munich, 5Institute for Neurosciences, TechnicalUniversity Munich, Germany

The importance of cytotoxic T cells (CTLs) in virus-induced immunopathology is widely acknowledged

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and also their role as effectors in autoimmunediseases of the CNS has become increasinglyrecognized. With regard to neurons as a target forCTLs, evidence was provided for antigen-specificinteraction by MHC class I restricted CD8+ T cellswith neurons in vitro. However, the case for epitope-specific interaction of CTL with neurons in vivo is lesswell established and remains controversial. Werecently established and characterized a new animalmodel that allows the analysis of molecularrequirements of CTL neuroaxonal interaction in vivo(Merkler et al., J. Clin. Invest., 2006): Neonatalinfection (first hit) with a genetically engineered andattenuated lymphocytic choriomeningitis virus(rLCMV/INDG) resulted in viral persistence exclusivelyin CNS neurons. Second infection in adulthood(second hit) with a LCMV Cl13 strain (LCMV Cl13)triggered a vigorous CD8+ T cell response of antiviralspecificity that resulted in severe CNS inflammationin rLCMV/INDG-carrier mice. In the present work,we dissected the contribution of different CTL effectormolecules Perforin, FAS-Ligand, Interferon-γ (IFN-γ) and TNF-α in mediating acute neuronal damage invivo. Histopathological analysis indicated that CTL-derived IFN-γ but not FAS or Perforin are essential forthe development of dendritic and synaptic alterationsand consequently disease precipitation during CTL-neuron engagement in vivo.

MODULATION OF THERMAL NOCI-CEPTION BY NGF AND SCF/C-KITSIGNALING

Nevena Milenkovic, Christina Frahm, CarolaGriffel, Bettina Erdmann, Carmen Birchmeier,Allistair Garratt, Gary R. LewinMax Delbrück Centrum für Molecular Medicine, Berlin,Germany

Sensory neurons in the DRG transduce diversesensory sensations like touch, heat and pain.Unmyelinated C-fiber axons represent about 60% ofDRG population and most are polymodal respondingboth to noxious thermal and mechanical stimuli.Neurotrophins are known to be involved in determingthe final phenotype of sensory neurons. To target thenociceptors the effect of NGF was suppressed in theearly postnatal period by injecting blocking antibodiesto NGF. This treatment led to a permanent change inthe phenotype of cutaneous sensory neurons bychanging the relative proportion of Aδ-delta-fibersand polymodal C-fibers. In addition CMH fibers hadelevated thermal thresholds (5oC higher thancontrols). Treated mice also displayed behavioralthermal hypoalgesia. DRGs were used for gene chipexpression analysis, and revealed 260 regulated genesin anti-NGF treated DRGs compared to controls.Large-scale in-situ analysis showed that some of thesetranscripts were expressed in sub-populations of DRGneurons. One of these genes - the receptor tyrosinekinase c-Kit - was functionally characterized. In DRG

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c-Kit is predominately expressed in small diametercells expressing TrkA and CGRP. Mice lacking afunctional c-Kit receptor displayed profound thermalhypoalgesia attributable to a marked elevation in thethermal threshold and reduction in spiking rate ofCMH nociceptors. Activation of c-Kit by SCF induceda profound potentiation of heat-activated currents in50% of isolated heat sensitive small diameterneurons. Acute application of SCF induced thermalhyperalgesia in mice and this action required TRPV1.SCF could potentiate capsaicin induced Ca2+ signalin a subpopulation of capsaicin sensitive cells. Thus,SCF/c-Kit signaling system has a key role in settingthe thermal threshold for activation of heat sensingnociceptive neurons.

ANALYSIS OF OPIOID RECEPTOR/K+ CHANNEL COUPLING INSENSORY NEURONS

D. Nockemann, C. Stein and P.A. HeppenstallCharité, Klinik für Anästhesiologie und operativeIntensivmedizin, Krahmerstr. 6-10, 12207 Berlin

Opioids are the most effective and widely used drugsin the treatment of severe pain. They act through G-protein-coupled receptors located on central andperipheral sensory neurons. Three classes of opioidreceptors (mu, delta, kappa) have been identified.Several mechanisms are involved in opioid analgesiaincluding G-protein-gated inwardly rectifying K+

(GIRK) channel activation and inhibition of voltage-gated Ca2+ channels. Interestingly, in peripheralsensory neurons Ca2+ channel inhibition has beenthe most studied mechanism and GIRK channelshave not been considered in any detail. The GIRKchannels form homo- or heterotetramericcomplexes, and are known to support the inhibitoryeffects of opioids in the central nervous system. Thesubunits GIRK1 and 2 have been found to beexpressed within the spinal cord dorsal horn, thecerebellum, the hippocampus and the cortex. Weare interested in whether GIRK channels are presentand whether opioids are coupled to GIRKs onperipheral sensory fibers. Furthermore, we willinvestigate the role of GIRK/opioid receptor couplingin a mouse model of inflammatory and neuropathicpain. To approach these questions, we are currentlyperforming quantitative RT-PCR, western blot and patchclamping experiments. We found no significantexpression of all 4 GIRK subunits in sensory neuronsusing RT-PCR and western blot. No change in theexpression level could be observed after inflammationof the mouse hindpaw. We also investigate functionalcoupling of GIRK channels and opioid receptors inperipheral sensory neurons using Patch clamping.We found no evidence for inward rectifying currentsin mouse DRG neurons, either before or aftertreatment with GIRK agonist DAMGO. Our dataindicate that GIRK channels are not present in sensoryneurons and do not contribute to peripheral analgesiaunder normal and inflamed conditions.

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64 DOES ENDOTHELIN-1 INDUCECORTICAL SPREADING DEPO-LARIZATION (CSD) VIA A DIRECTEFFECT ON THE VASCULATURE?

A. I. Oliveira-Ferreira2, M. Alam2, S. Major1,2, J. P.Dreier1,2

1Department of Neurology and 2Experimental Neurology,Charité University Medicine, Berlin, GermanyEndothelin-1 (ET-1) has attracted increasing interestsince its discovery by Yanagisawa in 1988.Recognized as a neuropeptide with neurotransmitter/neuromodulator functions, ET-1 is also one of themost potent vasoconstrictors. Moreover, it potentlyinduces CSD in vivo. ET-1 has been related toseveral pathophysiogical states in animals and humansassociated with the occurrence of CSD includingsubarachnoid hemorrhage, ischemic stroke andtraumatic brain injury. The mechanism by which ET-1induces CSD is scarcely understood. In order toanalyze whether induction of CSD by ET-1 is mediatedby its vasoconstrictive effect, we used a two cranialwindow model in rats (n=11). ET-1 was brain topicallyapplied in one window while the second one servedas control. DC/AC-electrocorticography (ECoG) andlaser-Doppler flowmetry were used to detect CSD.We observed a cluster of CSD starting from the ET-1 superfused window and propagating to the controlwindow. The cluster was associated with a negativeDC shift of –2.6+2.2mV on which transient negativeDC shifts of CSDs were riding. This was accompaniedby a positive DC shift of 0.9+0.9mV in the controlwindow superimposed with transient negative DCshifts. In another six experiments we recorded the pHchanges associated with ET-1-induced CSD usingpH-sensitive microelectrodes exhibiting initialacidification followed by a sharp alkaline shift typicalof ischaemic CSD. The pial arteries were imagedonto a camera to assess whether significantvasoconstriction precedes ET-1-induced CSD. Thiswas typically observed in some arteriolar segments.A detailed analysis is currently performed off-lineusing Image-J software. In conclusion, ourpreliminary data support the notion that ET-1 inducesischaemic CSDs due to its vasoconstrictive action.

RHOG IS A TARGET FOR MI-RNADEPENDENT REGULATION OFEXPRESSION AND HAS AN IM-PACT ON AXONAL BRANCHING

W. Otto, J. Baumgart, M. Dulinski, F. G.Wulczyn, R. Nitsch, and S. SchumacherInstitute of Cell Biology and Neurobiology, Center for Anatomy,Charité-Universitätsmedizin Berlin, Germany

RhoG is a member of the Rho family of smallGTPases. It was shown to be involved in the regulationof immune function, in processes of cell migration,phagocytosis, and neurite outgrowth induced by nervegrowth factor. RhoG activates Rac1 via a ternary

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complex containing ELMO and Dock180. Theexpression of RhoG in the brain is developmentallyregulated. One peak of expression in the rat cerebralcortex is around embryonic day 16. After declining,RhoG message is then upregulated again aroundpostnatal day 20. Although functional studies inneuronal cell lines suggested RhoG to be importantfor neurite outgrowth, its functional role in primaryneurons is not clear. Here we show that, in contrastto neuronal cell lines, RhoG does not seem to beinvolved in axonal outgrowth of primary hippocampalneurons. However, RhoG negatively regulates axonalbranching. Further, we bring evidence that RhoGexpression is regulated by the neuronal microRNAmiR-124, and that this regulation has functionalconsequences for axonal branching.Supported by a grant of the Deutsche Forschungs-gemeinschaft (SFB665-A2)

THE FUNCTION OF THE COX-SACKIEVIRUS-ADENOVIRUSRECEPTOR (CAR) IN THE DEVEL-OPING NERVOUS SYSTEM – ITSSELF-ASSOCIATION AND INTER-ACTION WITH ECM GLYCOPRO-TEINS

C. Patzke1, A. Dorner1, J. Behlke1, E. C. Müller1,A. Otto1, H. Schmidt1, S. Kröger2 and F. G.Rathjen1

1Max-Delbrueck-Center for Molecular Medicine, Berlin,Germany, 2Ludwig-Maximilian-Universität, Institut fürPhysiologie, München, Germany.

The coxsackievirus-adenovirus receptor (CAR), atransmembrane protein and member of theimmunoglobulin superfamily, is strongly expressedin the developing central nervous system and ispossibly involved in the formation of synapses oraxonal outgrowth. Antibodies to CAR blockattachment of neurons on glycoproteins of theextracellular matrix (ECM) or disturb neurite extensionon basal laminae preparations and in eye organcultures. Binding studies and affinity isolation of nativeCAR showed that fibronectin, laminin, fibulin-1,tenascin-R are extracellular interaction partners ofCAR. Interestingly the affinity of recombinant CAR tofibronectin is even higher (Kd: 100nM) than the affinityto the fiber knob protein of the adenovirus (Kd:140nM). We mapped the interaction to the heparin2/fibulin-1 binding-domain of fibronectin (283aa),which is different from the main integrin binding-segment, and to the second immunoglobulin-domain(D2) of CAR. Surprisingly, we observe homophilicbinding of CAR only when it is glycosylated, whereasheterophilic binding is also detected whenrecombinant CAR is expressed in bacteria. Besidethe CNS, CAR is also expressed on myotubes andthrough its interaction with agrin it might be crucialfor the generation of the neuromuscular junction.We assume that CAR acts, like integrins, as a linker

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between the ECM and the actin-cytoskeleton. Wefound that alpha-actinin is an intracellular bindingpartner of CAR. In mice deficient for CAR, theformation of the actin cytoskeleton is impaired.

CORTICAL GLUTAMATE ISLINKED TO REWARD RELATEDVENTRAL STRIATE ACTIVITY – ACOMBINED FMRI AND 1H-MRSSTUDY

C. Pehrs, J. Reuter, N. Klein, M. Voss, , T.Dembler, Y. GudlowskiBerlin Neuroimaging Center Project C2: F. Schubert1, R.Brühl1, F. Seifert1, Berlin Neuroimaging Center Project P12:J. Gallinat, A. Heinz, Charité Universitätsmedizin BerlinProcessing of rewarding stimuli is associated withincreased firing rate of dopamine neurons in theventral striatum, a core region of the brain rewardsystem. A close interaction between dopamine andglutamate has been proposed to play an importantrole in reward processing and in the pathophysiologyof schizophrenia. A correlation between the activityof the ventral striatum (BOLD contrast during rewardprocessing) and glutamate concentration in theanterior cingulate cortex in healthy subjects ishypothesized. 22 healthy subjects (age 19 to 46years) participated in a combined fMRI and MRSexperiment. In healthy subjects positive anticipationled to robust bilateral activation in the ventral striatum.Within the region of interest, multiple regressionanalysis shows activation in a cluster of 73 voxels onthe left side and 23 voxels on the right side to benegatively correlated with the concentration ofglutamate in the ACC. No significant positivecorrelations were observed and no significant corre-lations (positive or negative) were observed for thehippocampal glutamate concentration. Our resultsmay indirectly visualize an interaction of dopaminergicand glutamatergic neurotransmission which wouldbe highly relevant for schizophrenia research.

COMBINED ANTIDEMENTIVETREATMENT IMPROVES COG-NITIVE ABILITIES ONLY IN MCI-AD

Oliver Peters1, Doreen Lorenz1, Hans-JürgenMöller2, Lutz Frölich3, Isabella Heuser1

1Charité-CBF, Berlin; 2LMU, Munich; 3CIMH, Mannheim

Mild cognitive impairment (MCI) may represent earlystages of different neurodegenerative diseases. Themajority of the amnestic subtype (aMCI) is thought torepresent a prodromal stage of Alzheimers disease(AD). In a double-blinded placebo-controlled study237 aMCI were randomized to receive a combinationtherapy of Galantamin plus Memantine (Gal/Mem),Galantamine alone (Gal) or placebo (Plc). The studywas prematurely stopped during recruitment for safety).

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NKCC1-DEPENDENT GABAERGICEXCITATION DRIVES SYNAPTICNETWORK MATURATION DURINGEARLY HIPPOCAMPAL DEVELOP-MENT

Pfeffer C.(1,2), Stein V.(3), Keating D.(2), MaierH.(4), Rudhard Y.(2), Hentschke M.(5), Rune G.(6),Jentsch T.J.(1,2) & Hübner C.A.(2,5)

(1) Max Delbrück Centrum für Molekulare Medizin (MDC),Berlin, Germany ; (2) Zentrum für molekulare Neurobiologie,ZMNH, Hamburg, Germany ; (3) Max Planck Institut fürNeurobiologie, München, Germany ; (4) Dept. ofOtorhinolaryngology, University Hospital, Hamburg, Germany; (5) Dept. of Human Genetics, University Hospital, Hamburg,Germany ; (6) Dept. of Anatomy, University Hospital,Hamburg, Germany

Due to a high intraneuronal chloride concentrationGABA acts depolarizing in the immature brain and isthereby thought to sculpture the developing neuronalnetwork. We show that GABA-triggereddepolarization and Ca2+-transients were attenuatedin mice deficient for the Na-K-2Cl co-transporterNKCC1. Correlated Ca2+-transients and giantdepolarizing potentials (GDPs) were drasticallyreduced and the maturation of the glutamatergictransmission in CA1 delayed. Brain morphology,synaptic density, and expression levels of selecteddevelopmental marker genes were unchanged. Thesedata show that NKCC1-mediated Cl- accumulationcontributes to GABAergic excitation and networkactivity during early postnatal development and thusaccelerates the maturation of excitatory synapses.

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reasons, at that time aMCI were treated between 56-346 days. ADAS-cog was repetitively administeredwhile patients received study medication and afterdiscontinuation of treatment. 83 patients werereexamined two years after study entry. Analyzes ofthe etiologies underlying the aMCI syndrome revealedthat only patients with probable AD (MCI-AD) showeda significant cognitive benefit, while other etiologiesimproved only moderately. Improvement in the Gal/Mem group measured by ADAS-cog exceeded theeffect of treatment with Gal alone, while patientsreceiving Plc worsened (Gal/Mem: 1,08+5,38, Gal:0,29+2,67, Plc: -2+3,27; from baseline; sixmonths of treatment). After discontinuation oftreatment with Gal MCI-AD showed a significantcognitive decline (MCI-all: -1,82+4,85, MCI-AD: -2,67+3,5, from discontinuation baseline).Discontinuation of Mem showed no immediateworsening in ADAS-cog within one week. Two yearsafter the study had started 15% of aMCI hadconverted to dementia, all of them belonged to theMCI-AD subgroup and the majority of converterswas positive for APOE ε4. We conclude that onlyMCI-AD show a significant cognitive improvementand the combination therapy (Gal/Mem) exceededthe monotherapy (Gal

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FUNCTIONAL EFFECT OF AMUTANT OF THE SECONDEXTRACELLULAR LOOP OFCLAUDIN-5 IN THE BLOOD-BRAINBARRIER

C. Piehl, J. Piontek, L. Winkler, I. E. BlasigLeibniz-Institut für Molekulare Pharmakologie, Berlin,Germany

Tight junctions (TJs) of endothelial and epithelial cellsare the most apical component of the junctionalcomplex. They seal the paracellular space thusseparating different compartments for solutes. TJare organized as a network of intramembranousstrands, which are mostly comprised of claudins,occludin and junctional adhesion proteins. Studieson knock-out mice have demonstrated that Claudin-5 (Cld5) tightens the blood-brain barrier (BBB). Toinvestigate the role of selected amino acids of thesecond extracellular loop (ECL2) of Cld5 in tighteningthe paracellular space, we stably transfected Cld5-free MDCKII cells with Cld5wt or Cld5Y148A. The mutantshowed a loss of trans-interaction between Cld5proteins in the plasma membrane of opposing cells.To functionally characterize the impact of themutation, we measured the transepithelial electricalresistance (TER) of the transfected cells using twodifferent techniques. First, cells were seeded directlyonto gold electrodes of the ECIS system. We did notdetect a significant difference between the tightnessof Cld5wt-and Cld5Y148A-expressing cells. Second,the cells were seeded on filters allowing TERmeasurements with a conventional voltohmmeter. Incontrast to the ECIS system, a significantly higherTER was measured for Cld5wt than for Cld5Y148A.Furthermore, when compared to mock controls,the flux of fluorescein and 10°kDa FITC-dextranmeasured for Cld5wt and Cld5Y148A transfected cellswas decreased and increased, respectively. Theseresults indicate that (i) for our investigations the ECISsystem is less sensitive than conventional techniques.(ii) As Y148 is a key amino acid in the aromaticbinding core of Cld5-ECL2 causing the trans-interaction, this interaction is involved in the tighteningmechanism of the paracellular space of the BBB.

TOOLS FOR THE GENERATION OFSPECIFIC DRG CELL STRUCTURESIN VITRO.

Kate Poole, Jing Hu and Gary LewinMax Delbrück Center, Robert Rössle Str 10, 10119 Berlin.The cells of the dorsal root ganglion (DRG) exhibit adistinct morphology in vivo, with a single axon thatbifurcates at the dorsal root entry zone into twoarms. However, acutely cultured DRG cells do notspontaneously form similar structures in vitro. Weare using microcontact printing to pattern laminin onglass surfaces to culture cells in vitro with a structuresimilar to that observed in vivo. Microcontact printing

70 of proteins can be used to print proteins in specificpatterns at the micrometer scale. Printing of lamininon glass coverslips generates precise lamininstructures that are 10 nm in height. DRG cells can besuccessfully cultured on printed laminin, with the cellsavoiding the non-printed areas and the resulting cellshapes determined by the underlying pattern, includingbranching of neurites that are grown on lamininprinted in a T-junction structure. As well as 2D patterns,the technology used to create the masters used formicrocontact printing can also be used to generatemasters for the formation of substrates for cell culturethat include 3D topographical features. Such toolsallow questions about the influence of cell structureon function to be addressed.

SIRT1 CRITICALLY CONTRIBUTESTO THE REDOX-DEPENDENT FATEOF NEURAL PROGENITORS

Prozorovski, T.; Schulze-Topphoff, U.; Glumm,R.; Baumgart, J.; Schröter, F.; Ninnemann, O.;Siegert, E.; Bendix, I.; Nitsch, R.; Brüstle, O.;Zipp, F.; Aktas O.Charite Universitätsmedizin Berlin und MDC Berlin, Cecilie-Vogt-Klinik für Neurologie, Chariteplatz 1, 10117 BerlinIn the adult mammalian brain, multipotent and self-renewing neural progenitor cells (NPCs) have thecapacity to generate new neurons, astrocytes andoligodendrocytes. NPCs may thus serve as aregenerative tool with which brain damage can becompensated. However, repair processes in responseto many forms of neuronal injury, betheyinflammatory, ischemic, metabolic, traumatic orother, are characterized by a failure to replenishneurons and by a predominant occurrence ofastrocytes (known as astrogliosis). The possiblemolecular pathways underlying this phenomenon areonly poorly understood. Here, we show that subtlealterations of the redox state, found in different brainpathologies, substantially regulate the fate of murineNPCs via the histone deacetylase silent mating typeinformation regulation 2 homolog 1 (Sirt1). Mildoxidative conditions or direct activation of Sirt1suppressed proliferation of NPCs and directed theirdifferentiation towards the astroglial lineage at theexpense of the neuronal (and vice versa). Underoxidative conditions in vivo and in vitro, NPCsupregulated Sirt1, which then bound to the basichelix-loop-helix (bHLH) transcription factor Hairy/enhancer of split 1 (Hes1) and subsequently inhibitedthe proneuronal bHLH transcription factormammalian achaete scute homologue 1 (Mash1).Knock-down of Sirt1 by in utero electroporation ofNPCs prevented oxidation-mediated suppression ofneurogenesis, and upregulated Mash1 in vivo. Ourresults provide evidence for an as yet unknownmetabolic master switch which determines the fateof neural progenitors.

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CIRCADIAN RHYTHM IN PHONETICSPEECH PERCEPTION

Kathrin Pusch¹ ², Jessica Rosenberg¹, WernerSommer², Till Ronneberg³, Rainer Dietrich¹Humboldt University of Berlin, Department of GermanLanguage and Linguistics¹, Department of Psychology²,Ludwig-Maximilian University of Munich, Centre ofChronoscience and Systems Biology³

Some studies found time-dependent variation ofcognitive performance which was separate fromlapses in attention and psychomotor slowing (seeSchmidt et al. 2007). This could suggest circadianrhythm in cognitive functions. Our study investigateddifferences in speech processing, in particular speechperception, during the circadian cycle. Based on thetheory of Borbély (1982, see Schmidt et. al 2007)we predicted an increase of performance after acircadian nadir independent of vigilance andsleepiness. Twelve subjects performed a behaviouraldiscrimination task in a forced choice paradigm every3h during 40h of sustained wakefulness (ConstantRoutine protocol). Acoustic and phonetic stimuli werepresented binaural via headphones. Subjectivesleepiness was determined hourly, psychomotorvigilance every three hours. Salivary melatonin andbody temperature were used as circadian phasemarker. Best speech performance was found in theevening which was positive correlated with bodytemperature. After the circadian nadir associated witha central slowing without correlation of vigilance orsleepiness in the early morning performanceincreased again with a positive peak in the evening.We interpret this fact as a circadian drive. Longerreaction times and more lapses in phonetic perceptionindicate a higher task difficulty and a higher cognitivelevel compared to acoustic performance. Inconclusion, these results confirmed our hypothesisof circadian oscillation in speech processing, inparticular in speech perception, which could open anew direction for research of causes of languagedisorders.Schmidt C et. al (2007). A time to think: Circadianrhythms in human cognition. In: CognitiveNeuropsychology 24 (7): 755-78Supported by Daimler-Benz-Foundation Germany

DIFFERENCES IN REWARD PRO-CESSING ACROSS THE LIFESPAN

Rapp, M.A.1,2, Wrase, J. 1, Schlagenhauf, F. 1,Beck, A. 1, Schulte, S. 1,2, Gallinat, J. 1, & Heinz,A. 1

1 Charité Campus Mitte, Department of Psychiatry, Berlin, 2Geriatric Psychiatry Center, Charité Campus Mitte,Psychiatric University Clinic at St. Hedwig’s Hospital, BerlinIndividuals use the outcomes of their actions to adjustfuture behavior, and differential responses to bothgains and losses have been proposed across thelifespan. On a neurophysiological level, differentialactivation patterns in the striatum during reward

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processing have been shown in older adults. At thesame time, conceptual frameworks fromdevelopmental psychology suggest that fundamentalchanges in motivational structure and rewardprocessing may occur as early as midlife. We usedevent-related functional magnetic resonance imagingto determine whether young and middle-aged adultsdiffered in both self-reported and neuralresponsiveness to anticipated gains and losses. Thepresent study provides evidence for intact striatalactivation during gain anticipation in both groups,but shows a relative reduction in activation duringgain anticipation in middle-aged adults. Furthermore,striatal activation during gain anticipation was relatedto measures of fluid intelligence. These findingssuggest that changes in the processing of gains andlosses across the lifespan are reflected by functionalchanges as early as midlife, and may be related togeneral losses in fluid intelligence. Implications fordecision-making are being discussed.

ASTROCYTES RESPOND TO THECALYX OF HELD ACTIVITY

Daniel Reyes-Haro1, Jochen Müller1, TatjanaPivneva2, Christiane Nolte1, Joachim Lübke3 andHelmut Kettenmann1.1 Zelluläre Neurowissenschaften, Max-Delbrück-Centrum fürMolekulare Medizin, Berlin-Buch, Robert-Rössle-Str 10,13092 Berlin, Deutschland, 2 Bogomoletz Institute ofPhysiology, Bogomoletz St. 4, 01024 Kiev, Ukraine, 3 Institutfür Neurowissenschaften und Biophysik, INB-3,Forschungszentrum Jülich, 52425 Jülich, Deutschland

The medial nucleus of the trapezoid body located inthe brainstem is involved in sound localization andcontains the calyx of Held synapse (CoH), an axo-somatic giant synapse. Here we study thephysiological properties of astrocytes and theirinteraction with CoH. Astrocytes were easily identifiedin GFAP/eGFP transgenic mice. Whole-cellrecordings showed a linear current-voltage relationship(I-V) when repetitive de- and hyerpolarising 50 msvoltage pulses where applied. When biocytin wasincluded in the pipette, the dye spread to a networkof cells indicating that astrocytes are coupled. D-Asp(0.5 mM) triggered an inward current in astrocytesand this response was partially blocked by TBOA(100 µM) suggesting the expression of glutamatetransporters. Kainate (0.5 mM) mediated responseswere blocked by CNQX (25 µM) indicating theexpression of AMPA/kainate receptors. Stimulationof the afferent fibers to the MNTB also triggered aresponse in astrocytes, namely a slow inward currentand an intracellular calcium increase. Whenastrocytes were depolarised by voltage steps (from -70 to +50, the amplitude of the spontaneouspostsynaptic currents recorded in neurons wasincreased, suggesting a modulation of the CoH byastrocytes. To identify astrocytic compartments atthe electron microscopic level, the eGFP/GFAPtransgenic mice were labelled using antibodies against

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eGFP. Fine processes of astrocytes contact both,the pre- and postsynaptic membrane, but synaptic-like structures were never observed. These resultsshow that astrocytes sense CoH activity and modulatethe response in the postsynaptic cell.

KV7 (KCNQ) POTASSIUM CHANNELOPENERS ATTENUATE LEVODOPA-INDUCED DYSKINESIAS IN 6-OHDA-LESIONED RATS

A Richter* and SE SanderInstitute of Pharmacology and Toxicology, Faculty ofVeterinary Medicine, Freie Universität Berlin, Koserstr. 20,14195 Berlin, Germany, email: richtera@zedat.fu-berlin.deLevodopa-induced dyskinesias (LID) represent asevere complication of long-time pharmacotherapyin Parkinson’s disease that deserves noveltherapeutics. In the present study, the effects of theKV7.2-7.5 channel openers retigabine and flupirtinewere examined in comparison to amantadine (positivecontrol) in a rat model of LID. Compared with vehiclecontrols, retigabine (2.5, 5 mg/kg i.p.) and flupirtine(10 mg/kg i.p.) administered prior to levodopasignificantly reduced the severity of levodopa-inducedabnormal involuntary movements (AIM). Theantidyskinetic effect of retigabine (5 mg/kg) wascomparable to this of amantadine and was notaccompanied by severe adverse effects. The KV7.2-7.5 channel blocker XE-991 did not exert any effectson AIM at a dose of 1.5 mg/kg i.p., but antagonisedthe antidyskinetic effects of retigabine. At a higherdose of 3 mg/kg, XE-991 increased the dystoniccomponent of AIM. The results suggest that KV7channel openers, which have been reported to exertantiparkinsonian and analgetic effects, couldrepresent interesting candidates for the treatment ofLID. The antidyskinetic efficacy of the activators ofKV7.2-7.5 channels might be related to a suppressionof neuronal activity in the striatum. Further studiesare under the way to clarify whether retigabine andflupirtine delay or prevent the development of LID.

INTERLEUKIN—1BETA ANDNEUROTROPHIN-3 APPLICATIONFOR THE TREATMENT OF SPINALCORD INJURY

Rosenberger, K.; Hechler, D.; Skreka, K.;Nitsch, R. & Hendrix, S.Institute for Cell Biology and Neurobiology, Center forAnatomy, Charité-Universitätsmedizin Berlin, Germany

Traumatic injury of the spinal cord is followed by aneuroinflammatory wound healing response.Previously, we demonstrated that pro-inflammatorycytokines influence neurotrophin-induced axonaloutgrowth of dorsal root ganglia in a dose-dependentmanner. In the present study, we address the question

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of whether cytokines modulate neurotrophin-inducedaxonal regeneration after CNS injury in vitro and invivo. Using an organotypic cortex outgrowth assay,we demonstrated that neurotrophin-3 (NT-3) and thepro-inflammatory cytokines IL-1beta (IL-1b), IL-6 andTNF-alpha significantly promote axon elongation anddensity. The combination of recombinant IL-1b andNT-3 significantly stimulate axon outgrowth comparedto NT-3 alone. Interestingly, IL-1b deficiency had noinfluence on axon growth suggesting that endogenousIL-1b is not necessary for spontaneous neuriteelongation. Recombinant IL-1b significantly increasedthe axonal length of primary neurons, indicating adirect effect on neuronal cells. In a similar outgrowthassay using organotypic transverse slices of mouseE13 spinal cords IL-1b and NT-3 could not increaseaxonal outgrowth. However a significant inhibitionof axon growth by the pan-neurotrophin receptorblocker K252a suggests that maximal outgrowth isalready induced by endogenous neurotrophins.Furthermore, we investigated the impact of IL-1b onNT-3 therapy after spinal cord injury (SCI) in vivo.NT-3 has already been successfully applied in severalin vivo models of SCI, leading to axonal sproutingund functional recovery in rats. Thus, we establisheda mouse model of NT-3 therapy after contusionSCI. The local application of IL-1b was lethal,however, IL-1b deficient mice with and without NT-3administration showed significantly better clinicaloutcome after SCI compared to wildtype controlmice.

A SELF-MADE MEDIUMSUPPLEMENT FOR PRIMARYNEURONAL CULTURE REVEALSTHE ROLE OF SELENIUM FORNEURONAL SURVIVAL

Stephan Roth1, Eva K. Wirth1 and UlrichSchweizer1

1Neurobiology of Selenium, Neuroscience Research Center,Charité-Universitätsmedizin Berlin

Mice with compromised selenoprotein expression inneurons suffer neurodegeneration. Selenoproteinsare proteins containing the rare amino acidselenocysteine. There are 24 genes encodingselenoproteins in the mouse, most of which areneuronal expressed. Selenoprotein expression is mostprominent in hippocampal, cortical, and cerebellarneurons. The selenium transport protein,selenoprotein P has been purified as a neurotrophicfactor from calf serum, but can be functionallyreplaced in culture by sodium selenite, a common,but non-physiological, supplement for neuronal cellculture. Investigating the roles of selenoproteins inneurons is hampered by the fact that commercialB27 supplement contains selenite and a cocktail ofother antioxidants, including enzymes like catalaseand superoxide dismutase. To establish a cell culturemodel suitable for the study of selenium effects in

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neurons, we have re-investigated the constituents ofB27 and show that our self-made supplement yieldscomparable survival rates as B27. We show that theEC50 value of H2O2 is only about 40µM in mediumlacking catalase as compared to 300µM in mediumcontaining catalase (as B27). Moreover the effectof gene inactivation of Gpx4, a selenium-dependentphospholipid hypdroperoxide peroxidase, is maskedin neurons by excess vitamin E in the culturemedium.Using several inductors of cell death in vitro,like H2O2, glutamate or SIN-1, we demonstrated theprofound modulation of cell survival by seleniumcontent of the culture medium. In summary, we havenow established a unique cell culture model in whichwe can dissociate the effect of selenium and otherantioxidants from each other. In contrast, such studiesare not feasible using commercial media alreadycontaining a high-dose mix of antioxidants.

COMBINATION OF DC-MAGNETO-ENCEPHALOGRAPHY AND TIME-RESOLVED NEAR-INFRAREDSPECTROSCOPY FOR THE STUDYOF NEURO-VASCULAR COUPLING

T.H. Sander1, S.Leistner2, H. Wabnitz1, M.Burghoff1, G. Curio2, B.M. Mackert2,3, R.Macdonald1, L. Trahms1

1 Physikalisch-Technische Bundesanstalt, Berlin, 2 Dept. ofNeurology, Charité Campus Benjamin Franklin, Berlin, 3 Dept.of Neurology, Vivantes Auguste Viktoria Klinikum, Berlin;Germany

The knowledge of the temporal relation betweenneuronal activity and the accompanying response inthe vascular system of the brain may foster a betterunderstanding of fMRI in basic research and clinicalapplications. To this end, we have combined DC-magnetoencephalography (DC-MEG) and time-resolved near-infrared spectroscopy (trNIRS) tomeasure simultaneously cortical neuronal andvascular activations during finger movements in 12subjects. In contrast to earlier studies, the modulationDC-MEG has been replaced by a broadbandunmodulated DC-MEG and the temporal resolutionof the combined setup is refined up to tens of ms.The subjects were asked to repeat a sequence of 30s of finger movements followed by 30s of rest for30 times. Independent component analysis (ICA)was applied to extract the stimulus related signalcomponents at 0.0166 Hz (1/ 60 s-1) from the DC-MEG and trNIRS data. ICA extracted the stimulusrelated signal best if the bandwidth of the data wasreduced to 8 Hz. This indicates that the ICAassumptions are violated by, e.g., noise contributionsor a number of additional sources above 8 Hz suchas alpha-oscillators. This bandwidth reduction stillallows to study the relevant processes as the transitiontime for the neuronal DC-MEG signal between restand movement period is around 0.5 s contrastingwith a transition time of several seconds in the vascularsignals recorded by trNIRS.

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Supported by DFG through grant BA 1222/6-1,BMBF Grant 01 GO 0208, GF GO 01184601,01 GO 0503 and 01 GO 0518, Berlin Neuro-imaging Center.

DRUG RESISTANCE IN THE HUMANEPILEPTIC HIPPOCAMPUS ANDTEMPORAL CORTEX

N. Sandow1, S. Kim1, C. Raue1, D. Päsler1, L.Leite Antonio2, R. Kovacs1, P. Fidzinski1, M.Alam1+, Z.-J. Klaft1, U. Heinemann1, S. Gabriel1,and T.-N. Lehmann1*

1Institute of Neurophysiology, 1*Department of Neurosurgeryand 1+Department of Neurology, Charité-University MedicineBerlin, Berlin, Germany; 2Neurologia Experimental,Universidade Federal de Sao Paulo-Escola Paulista deMedicina, Sao Paulo, Brazil

Epileptiform activity could be induced in the dentategyrus (DG) of hippocampal slices from surgicallyremoved tissue of patients suffering from drugresistant mesial temporal lobe epilepsy (MTLE)(Gabriel et al. 2004). Furthermore, we showed thatthe in vitro-epileptiform activity in the DG – like seizuresof long-time drug resistant MTLE-patients - is resistantto the antiepileptic drug carbamazepine (Jandova etal. 2006). In the present study we investigated effectsof valproate (VPA, 1mM) and carbamazepine (CBZ,50µM) on epileptiform activities in two differenthippocampal regions (DG, Subiculum: 10-12mM[K+]o) and in the temporal cortex (TCx) (8mM [K+]oand 50uM Bicuculline). Data were obtained from120 recordings (32 patients). After 30 minutesperfusion with CBZ or VPA, epileptiform activity wascompletely suppressed in 3.3% of recordings (6.3%of patients). Ictal-like activity was replaced by inter-ictal spiking in 6.7% of recordings (3.1% of patients)or remained unaltered in 90% of recordings (90.6%of patients). In the last sample, event-amplitudes wereslightly but significantly reduced while drug effects onevent-duration, intra-event discharge frequency, andevent-rate could not be proven significant. Therewere no differences of effects between hippocampusand TCx and between CBZ and VPA, indicating thatfocal epileptic tissue with open blood brain barrier isdrug resistant on behalf of mechanisms located inthe parenchyma.Supported by a grant of the DFG SFB T3 to TNL andUH and by CAPES Brazil to LLA

TOLL-LIKE RECEPTOR 4/MYD88PATHWAY MEDIATES THE MICRO-GLIAL PROINFLAMMATORYRESPONSE TO THROMBIN-ASSO-CIATED PROTEIN COMPLEXES

Jörg Scheffel, Denise van Rossum1, JonathanR. Weinstein2, Hassan Dihazi3, Tommy Regen1,Wolfgang Brück1, Helmut Kettenmann4, MarcoPrinz1, Thomas Möller2 and Uwe-Karsten Hanisch1

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1 Institute of Neuropathology, University of Göttingen,Göttingen, 2 Department of Neurology, University ofWashington, Seattle, 3 Institute of Nephrology andRheumatology, University of Göttingen, Göttingen, 4 CellularNeurosciences, Max Delbrück Center for MolecularMedicine, BerlinThrombin, the central blood coagulation factor, exertsa multitude of cellular effects through limitedproteolysis of protease-activated receptors (PAR). Thismechanism is also considered for the induction ofproinflammatory mediators in microglia. Challengingthis notion, we identified a minor high molecularweight (HMW) protein fraction as the sole andextremely potent carrier of this activity in thrombinpreparations. The HMW fraction contains mature ¾yet enzymatically inactive ¾ thrombin presumablywithin a plasma/coagulation protein complex. Weshow now that microglial activation by thrombinHMW

critically depends on Toll-like receptor 4 (TLR4) andassociated MyD88 signaling, with additional receptor/signaling pathways providing contributions. On theother hand, PARs, alternative thrombin receptors,proteolytic thrombin activity and functional domainsare either not mandatory or even dispensable.Biochemical analyses, mass spectrometry andfunctional characterization revealed fibronectin as amicroglia-stimulating thrombinHMW constituent withTLR4-agonistic capacity. Importantly, bacteriallipopolysaccharide as a common microbial TLR4agonist can be ruled out as a confoundingcontaminant. Our findings identify the essential ligand-receptor mechanism underlying the thrombin/PAR-assigned proinflammatory responses in microglia.They may request a careful revision of other cellularactivities previously established for thrombin. Mostimportantly, they indicate a role for TLR4-centeredsignaling in the activation of microglia by plasma-derived protein complexes upon vascular impairment.This novel mechanism especially supports theemerging concept of coagulation cascade-drivenCNS damage in diseases like multiple sclerosis.Supported by DFG.

NONVIRAL TRANSFECTIONENABLES STABLE GENE TRANS-FER INTO MURINE MESENCHYMALSTEM CELLS DERIVED FROMBONE MARROW

F. Scheibe1,2, J. Priller 1,2

1Department of Experimental Neurology, 2Laboratory forMolecular Psychiatry, Charité – University Medicine Berlin,Germany

Mesenchymal stem cells (MSCs) from bone marrowhave been used for therapeutic purposes in a varietyof mouse models for neurological disorders.Powerful technologies for genetic modification ofthese cells offer their potential use in regenerativemedicine and cyto –and gene therapy. MSCs wereisolated from bone marrow of adult C57BL/6 mice

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and were characterized by their differentiation potentialinto adipocytes, osteoblasts and chondrocytes andby FACS analysis for their surface marker expression.We aimed to determine whether mMSCs can begenetically modified by ex vivo gene delivery usingthe following transient transfection procedures:nucleofection, magnetofection and lipofection.mMSCs were transfected with the pEGFP-N2 plasmidvector and were analysed by FACS for EGFP signalling48hr after transfection. Results indicate thatnucleofection is the most efficient procedure fortransient gene delivery into mMSCs, followed bymagnetofection and lipofection. By selection withG418 disulfate and use of single cell – colony formingunit (sc-CFU) assay transiently transfected mMSCsbecame stably transfected for EGFP by all threetransfection methods without loss of their stem cellplasticity. Moreover, murine erythropoietin (mEPO)was introduced into mMSCs. Cells stably integratedmEPO into their genome and secreted high amountsof mEPO for several weeks as detected by ELISA.Hematopoietic activity of mMSC derived mEPO wassuccessfully assessed by CFU-E (colony formingunit – erythroid) assay. In summary, transienttransfection methods are sufficient to generate stabletransfected mMSCs that might be a source to developtreating strategies of a variety of disorders like stroke,parkinson´s disease or myocardial infarction.Supported by a grant of the Bundesministerium fürBildung und Forschung to JP.

ASTROCYTES IN SITU RESPONDTO THE ANTI-DEPRESSANT CITA-LOPRAM INDEPENDENT FROMNEURONAL ACTIVITY

C. G. Schipke, I. Heuser, O. PetersDepartment of Psychiatry and Psychotherapy, CampusBenjamin Franklin, Charité-Universitätsmedizin Berlin

An active role for astrocytes in memory processingis more and more recognized, but their role in mooddisorders has yet to be elucidated. Thepathophysiological basis of major depressive disorder(MDD) and the mode of action of anti-depressantdrugs are not completely understood. One importanttarget in the treatment of MDD is the serotonine (5-hydroxytryptamine, 5-HT) system and selectiveserotonine reuptake inhibitors (SSRIs) are widely usedto treat the disease. Interestingly, for astrocytes, adysfunction in glutamatergic pathways was found inMDD. We loaded astrocytes in acute slices of themouse prefrontal cortex with the calcium-sensitivedye Fluo-4 and analyzed the astrocyte calciumresponses to stimulation with the SSRI citalopram or5-HT directly. We found that in acute slices of themouse prefrontal cortex, citalopram, as well as 5-HT itself induce calcium signals in a subset ofastrocytes also in the presence of tetrodotoxin (TTX).The calcium transients in individual astrocytes occurdelayed and not all at once, in contrast to responses

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to ATP or glutamate. These delayed calciumresponses were also observed after the applicationof the 5HT1- and 5HT2-receptor agonists 5-Carboxyamidotryptamine and alpha-Methyl-5-hydroxytryptamine, respectively. Responses to 5-HTcould mostly not be evoked twice. This effect wasdiminished in the presence of TTX, and we determinedglutamate as a modulatory substance: 1) after acalcium response evoked by glutamate, astrocytesdo not show a response to 5-HT and 2) applicationof CNQX restores the ability to exhibit a secondresponse to 5-HT. Thus, responses to stimulation ofglutamatergic and serotonergic receptors onastrocytes are functionally interfering and astrocytesmight link serotonergic and glutamatergic functionsin the pathophysiology of MDD.

EVALUATION OF THE RAT FREEEXPLORATORY BEHAVIOUR AS ANANIMAL TEST FOR TRAIT ANXIE-TY IN RATS

Rex, A., Schmidt, N., Voigt, J.P.*, Bert, B., Fink,H.Institute of Pharmacology and Toxicology, School of VeterinaryMedicine, FreieUniversität Berlin, Koserstr. 20, 14195 Berlin,Germany, *University of Nottingham, School of VeterinaryMedicine and Science, Sutton Bonington Campus, SuttonBonington, Leicestershire, LE12 5RD, UK

The free exploratory paradigm is regarded as areliable test for trait anxiety in mice (Griebel et al.,Behav Pharmacol 1993, 637-644) but it may beuseful in the research for the neurobiological basisof anxiety in rats, too. Previously we could show thatrat strains differ in their desire for non-forcedexploration of novel areas, like the surroundings oftheir familiar cage when the grid-covers of the cagewere removed (Rex et al., Pharmacol Biochem Behav1996, 107-11). Now, we evaluated this testbehaviourally using naïve Sprague Dawley and Wistarrats obtained from different sources. Sprague Dawleyrats were tested at the age of 30, 55, 78 and 110days. Evaluation also included assessment of seasonalvariation, sex-specific impact and habituation to thetest. Additionally, the test was evaluatedpharmacologically using diazepam (1, 2 mg/kg IP)and caffeine (50 mg/kg IP). Parameters measured:The latency to the first escape within 10 min, thepercentage of rats exploring the outside and thenumber of the escapes. Latency to the first escapewas the most reliable and sensitive parameter.Seasonal variability of the latency to the first escapewas low. Rat strains and sexes differ in the latencytoo, while age-related differences have less impact.Diazepam (2 mg/kg) decreased and caffeine (50mg/kg) increased the latency to explore the outside ofthe cage. We conclude that the free exploratorybehaviour can be used to study anxiety-relatedbehaviour in rats.

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85 STIMULUS DEPENDING CHANGESOF EXTRACELLULAR GLUCOSE INTHE RAT HIPPOCAMPUSDETERMINED BY IN VIVOMICRODIALYSIS

Rex, A.; Bert, B.; Fink, H.; Voigt, J.P.*Institute of Pharmacology and Toxicology, Freie UniversitätBerlin, Koserstr. 20, 14195 Berlin, Germany, *University ofNottingham, School of Veterinary Medicine and Science,Sutton Bonington Campus, Sutton Bonington, Leicestershire,LE12 5RD, UK

Neuronal activity is coupled to brain energymetabolism with glucose being an important substrate.We assessed extracellular glucose concentrations inthe rat ventral hippocampus during anxiety-relatedbehaviour. Determination of basal hippocampalglucose and lactate/pyruvate ratio in male Wistarrats was conducted in the home cage using in vivomicrodialysis. Rats were exposed to the elevated plusmaze, a test for anxiety or to one out of two differentcontrol conditions: i) unspecific stress induced bywhite noise (95 dB) or ii) presentation of foodfollowing a 10 hrs fasting period. Basal levels ofglucose, determined using zero-net-flux, and the basallactate/pyruvate ratio were 1.48+/-0.05 mmol/l and13.8+/-1.1, respectively. In rats without manipulationglucose levels remained constant throughout theexperiment (120 min). Exposure to the elevated plusmaze, however, led to a temporary decline inhippocampal glucose (-33.2+/-4.4%) whichreverted to baseline within 10 minutes after return tothe familiar home cage. White noise decreasedextracellular glucose level (-9.3+/-3.5%) non-significantly. In hungry rats, immediately afterpresentation of food, a significant reversible drop inhippocampal glucose levels (-19.7+/-5.9%) wasdetermined for about 10 minutes. In all groups, thelactate/pyruvate ratio remained unchanged by theexperimental procedures. Our microdialysis studydemonstrates that exposure to the elevated plus maze,but also to food induces a transient decrease inextracellular hippocampal glucose concentration. Incontrast, an unspecific stimulus did not changehippocampal glucose. The latter suggests that onlyspecific behavioural stimuli increase hippocampalglucose utilization in the ventral hippocampus.

METABOLIC CONSEQUENCES OFCAVEOLIN 3 MUTATIONS

Saskia Schmidt1, Anja Mähler2, MichaelBoschmann2, Mario Hermsdorf2, Marc-AndréWeber3, Simone Spuler1

1Muscle Research Unit and 2Franz-Volhard-Center of theExperimental and Clinical Research Center (ECRC), CharitéUniversity Medicine Berlin and MDC, Berlin, Germany,3Department of Radiology, German Cancer Research Center,Heidelberg, Germany

Objectives: Caveolae are small invaginations of thecell membrane important in compartmentalization

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of signal transduction pathways. In neurons, allisoforms of caveolin are expressed and appear tobe involved in regulation of neurotrophin signaltransduction, neurite sprouting and synaptogenesis.In skeletal muscle, only caveolin 3 is found. Mutationsin caveolin 3 (CAV3) lead to a variety of muscledisorders, including limb girdle muscular dystrophy1C,rippling muscle disease and hyperCKemia. Apart fromfixed weakness the patients complain of lack ofendurance and myalgias. Cav3-knockout mice haveimpaired glucose resistance. We asked whetherskeletal muscle of patients with CAV3 mutations maybe functionally altered in terms of glucose utilisation.Methods: Six probands with defined CAV3 mutationsand ten controls were examined. A metabolic profilewas obtained from all probands under restingconditions and during exercise. This consisted ofglucose and fatty acids metabolites during an oralglucose tolerance test (ogtt) while microdialysis ofskeletal muscle and adipose tissue was performed.Functional MR-imaging of skeletal muscle included13P, 23Na, 1H and whole-body-MRI. In addition, glucoseuptake was measured in vitro in primary myoblastcultures from probands with CAV3 mutations andcontrols.Results: In vivo, in CAV3-deficient skeletal musclewe found significantly decreased glucose uptakeduring ogtt than in controls. Lactate was significantlyelevated, whereas pyruvate, the metabolite of theanaerobic glucose oxidation, was significantlydecreased. Blood flow as determined by ethanolratio was reduced in diseased muscle. These findingswere specific for skeletal muscle and were not seenin adipose tissue. In MR-imaging, the 1H-spectra ofCAV3-deficient skeletal muscle detected only theintracellular lipid compartment while they failed todemonstrate extramyocellular lipids. In vitro myoblaststudies are in progress.

EFFECTS OF UNCERTAINTY ONPERFORMANCE MONITORING INOLDER ADULTS

Melanie Schreiber, Norbert Kathmann, TanjaEndrassHumboldt University, Berlin, Germany

Event-related brain potential (ERP) studies identifiedthe error related negativity (ERN/Ne) and the correctrelated negativity (CRN) to be related to performancemonitoring. It has been repeatedly found that ERN/Ne amplitudes are attenuated in older compared withyounger adults. Our previous research also showedage-related alteration in correct trials: the CRNamplitude was enhanced in older participants. Apattern of reduced ERN/Ne and enhanced CRNamplitudes has been associated with high decisionuncertainty. The present experiment aimed toinvestigate whether age differences in ERN/Ne andCRN amplitudes are related to higher task uncertaintyin older adults. Participants performed a visual

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discrimination task with four difficulty levels (veryeasy, easy, difficult, very difficult) to examine decisionuncertainty while recording event-related potentials.They were asked to discriminate the size of two dotsand to decide which one of these dots was larger.Subsequent response accuracy ratings (correct,incorrect or uncertain) allowed us to compare awareand unaware correct and incorrect reactions as wellas trials classified as uncertain. ERN/Ne and CRNamplitudes were reduced in older compared toyounger adults. Both groups showed attenuated ERN/Ne amplitudes with higher task difficulty. While inyounger adults CRN amplitudes increased with highertask difficulty the CRN did not change in older adults.The percentage of uncertainty ratings did not dependon age. Further the distribution of uncertainty ratingscorresponded not to the course of the CRN in thedifferent task conditions. Whereas ERN/Ne amplitudeswere attenuated with higher task difficulty in both agegroups, only younger adults also showed a variationof CRN amplitudes. Thus, the present results indicatethat age effects of ERN/Ne and CRN amplitudesseem not (only) to be due to decision uncertainty.

NOW YOU’LL FEEL IT – NOW YOUWON’T: PRE-STIMULUS EEGCORRELATES OF CONSCIOUSPERCEPTION

Ruth Schubert1,2, Stefan Haufe3,4, FelixBlankenburg5, Arno Villringer2,6, Gabriel Curio1,2

1. Neurophysics Group, Charité – University Medicine Berlin,Campus Benjamin Franklin, Hindenburgdamm 30, 12203Berlin, Germany, 2. Berlin NeuroImaging Center, Charité –University Medicine Berlin, Campus Charité Mitte,Charitéplatz 1, 10117 Berlin, Germany, 3. Fraunhofer FIRST(IDA), Kekulestrasse 7, 12489 Berlin, Germany, 4. MachineLearning Group, Technical University Berlin, Franklinstr. 28/29, 10587 Berlin, Germany, 5. Bernstein Center forComputational Neuroscience, Charité, Philippstr. 13, 10115Berlin, Germany, 6. Max-Planck-Institut für Kognitions- undNeurowissenschaften, Stephanstraße 1a, 04103, Leipzig,Germany

A multitude of environmental events impinge on thereceptor surfaces of our senses, yet only a minorfraction of them is perceived consciously. If severalstimuli arrive at our sensors concomitantly, competingfor an access to conscious perception, we cannotbuild a conscious percept of many even supra-threshold stimuli embedded in a context of moresalient stimuli (masking). This raises intriguingquestions about where and how in our brains theperceptual fate of a particular stimulus is determined.Using the high temporal resolution of EEG, weinvestigated the neuronal mechanism precedingconscious perception of supra-thresholdsomatosensory stimuli at the left index finger followedby stimuli of higher intensity at the right index finger(backward masking). The detection rate for the leftindex finger stimuli declined from 75 % whenpresented alone to 32 % when followed by a masking

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stimulus. We identified two EEG signatures predictivefor the access to somatosensory awareness: (i) 500ms preceding an consciously perceived stimulus theleft frontal cortex becomes active as indexed byregional beta rhythm (~ 20 Hz) desynchronization,(ii) an attenuation of mu (~ 10 Hz) and beta ‚idling‘rhythms is found at those pericentral sensorimotorcortices that are going to process the upcomingtarget stimulus. Furthermore, the individual level ofpre-stimulus mu- and beta band amplitudes over thefrontal and somatosensory cortex is crucial for theproportion of perceived stimuli in a masking context.We suggest an activation of left frontal areas involvedin top-down attentional control critical for screeningagainst backward masking that leads the preparationof primary sensory cortices: The ensuing suppressionof sensory idling rhythms may provoke a strongerneuronal response to the upcoming stimulus andtherewith effectively promotes conscious perceptionof supra-threshold stimuli embedded into anecologically relevant condition featuring competingenvironmental stimuli.

PERFORMANCE MONITORING ANDDECISION-MAKING IN PATIENTSWITH BORDERLINE PERSONALITYDISORDER

Schuermann, B.1, Kathmann, N.1, Renneberg,B.2, & Endrass, T.1

1Department of Clinical Psychology, Humboldt-UniversitätBerlin, Germany, 2Department of Psychology, JohannWolfgang Goethe-Universität, Frankfurt a. M., Germany

Marked impulsivity is considered to be a corecharacteristic of borderline personality disorder (BPD)and has been shown to play a significant role indecision-making and planning. In line with this notion,neuropsychological studies have found alterationsin these executive functions which are related todysfunctions of the prefrontal cortex in BPD. Despitethe clinical relevance of decision-making in BPD,the number of studies investigating itsneurophysiologic correlates is still small. In the presentstudy, decision-making was examined in patients withBPD and matched healthy controls while performinga modified version of the Iowa Gambling Task (IGT)and an electroencephalogram was recorded. TheIGT is a neuropsychological task designed to studymechanisms of diminished impulse control and risk-taking behaviour which relates to imbalanced activitybetween the prefrontal cortex and the amygdala. Theclinical impression indicates that patients with BPDshow alterations in negative feedback processing.Hence, an objective was to examine performancemonitoring in patients with BPD by measuring thefeedback negativity. The behavioural results suggestthat patients with BPD showed less advantageousand more risky choices on the IGT than did thehealthy controls. The ERP analysis indicatedimpairments in negative feedback processing in

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patients with BPD since feedback negativity wasreduced. The attenuated feedback negativity reflectsreduced action monitoring in patients with BPD andsuggests dysfunctions of the ACC. In contrast,processing of outcome probability and value wasnot affected in BPD. However, since the study is notyet completed, the results are preliminary.

EXPRESSION OF A CALCIUMSENSOR PROTEIN IN MICROGLIA

Seifert S, Färber K, Uckert W and Kettenmann HDept. of Cellular Neurosciences, Max-Delbrück-Center,13122 Berlin, GermanyMicroglial cells express a variety of neurotransmitterreceptors. Activation of these receptors can lead toCa2+ influx into the cytoplasm by release from internalstores or by opening channels in the cytoplasmicmembrane. We have previously studied microglialCa2+ signals in vitro using Ca-sensitive dyes, but sofar Ca2+ signals in microglial cells in situ could notbe analyzed since we (and others) have not found aprocedure to load the cells with Ca2+ indicators. Toovercome this restriction we have employed a Ca2+-sensitive genetic construct G-CaMP2 [Tallini et al.,PNAS. Vol. 103 (2006) 4753-58]. GCaMP2 is afusion protein of GFP, calmoduline and a myosinchain. Ca2+-dependent fluorescence changes resultfrom the interaction between Ca2+/calmodulin at theC terminus of circularly permuted GFP and an N-terminal myosin light chain kinase fragment. Aftertransfection of primary microglia cells with the vectorp-N1-G-CaMP2 using electroporation, we foundGCaMP2 expression in more then 50% of cells.Moreover we can demonstrate that 48h aftertransfection, these microglial cells show anintracellular Ca2+ increase evoked by ATPapplication. When we added transfected microgliato an organotypical slice culture, we can also detectintracellular Ca2+ signals in response to ATP 48hafter transfection. Since transfection of microglialcells by using electroporation is limited to cell culture,we created a retroviral vector expressing the calciumsensor protein G-CaMP2. By using this experimentalapproach, we could transfect cultured microglial cellwith an efficiency of 35%. We were also able totransfect cells in organotypical slices. Our datashow that the expression of the Ca2+ sensitive proteinG-CaMP2 will be a useful tool for recordingintracellular Ca2+ signals in microglial cells in situ.

IN VIVO IMAGING OF LYMPHO-CYTES IN THE CNS REVEALSDYNAMIC T CELL COMPARTMEN-TALIZATION

Siffrin, V.; Brandt, A.U.; Radbruch, H.; Herz, J.;Boldakowa, N.; Leuenberger, T.; Werr, J.;Schulze-Topphoff, U.; Nitsch, R.; Zipp, F.

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Charité - Universitätsmedizin Berlin und MDC Berlin,Cecilie-Vogt-Klinik für Neurologie, Charitéplatz 1, 10117BerlinIn the course of autoimmune CNS inflammation,inflammatory infiltrates form characteristic perivascularlymphocyte cuffs by mechanisms that are not yetwell understood. Here, intravital two-photon imagingof the brain in anesthetized mice with experimentalautoimmune encephalomyelitis (EAE) revealed thehighly dynamic nature of perivascular immune cells,refuting suggestions that vessel cuffs are the result ofa shortage of lymphocyte motility in the CNS. Onthe contrary, vessel-associated lymphocyte motility isan actively promoted mechanism which can beblocked by CXCR4 antagonism. In vivo blockade ofCXCR4 in EAE disrupted dynamic vessel cuffs andresulted in invasive random migration. Furthermore,CXCR4-mediated perivascular lymphocyte movementalong CNS vessels was a key feature of CD4+ T cellsubsets in contrast to motility in CD8+ T cells,indicating a dominant role of the perivascular areaprimarily for CD4+ T cells. We defined a new marker,the vector-vessel angle, which objectified this CNSspecific behavior of CD4+ T cells and reliablydemarcated it from random migration as seen inCD8+ T cells. Our results visualize dynamic T cellmotility in the CNS in the living animal and demonstratedifferential CXCR4-mediated compartmentalizationof CD4+ T cell motility within the healthy and diseasedCNS.

A MOLECULAR DISSECTION OFTRPV1 SENSITISATION USING THENAKED MOLE-RAT

Ewan. St.J. Smith, Gireesh. Anirudhan, and GaryR. LewinDept. of Neuroscience, Max-Delbrueck Centrum, Berlin-Buch, Germany

Tissue inflammation leads to pain and behavioralsensitization to thermal and mechanical stimuli calledhyperalgesia. However, the African naked mole-rat(NMR, Heterocephalus glaber), has behavioralinsensitivity to capsaicin and acid. Additionally, nervegrowth factor (NGF) fails to induce thermalhyperalgesia, a phenomenon dependent uponTRPV1. We aimed to discover why NGF fails toinduce thermal hyperalgesia in NMRs. In mouse theisolectin B4 (IB4) labels TrkA negative DRG cellsand immunocytochemistry demonstrated the samepattern in NMR DRG cells. NGF sensitized thecapsaicin-gated current in mouse DRG neurons thatwere IB4-ve (n = 11), but failed to do so in eitherIB4+ve or IB-ve NMR DRG neurons (n = 14).Cloned NMR TRPV1 possesses the Y200 residuethat in other species is fundamental for NGF-inducedsensitization in TRPV1. When expressed in CHOcells NMR TRPV1 is activated by heat, capsaicin, pHand voltage in a similar fashion to TRPV1s fromother species. We introduced NMR TRPV1 into DRGneurons from TRPV1-/- mice and in this context

NGF caused potentiation of NMR TRPV1 in IB4-veneurons (n = 8). This data suggests that there issomething about NMR cells or NMR TrkA that isresponsible for the lack of sensitization observed.To determine if the cellular environment is critical forNGF induced sensitization, a new fibroblast cell linewas established from NMR kidney tissue. Four cloneswere isolated and have reached population doublingsin excess of 40. We are using these cells to test thehypothesis of whether the cellular environment ofNMR cells is responsible for the lack of NGF inducedsensitization. To conclude, NGF fails to sensitizeNMR TRPV1, which may account for the lack ofNGF-induced thermal hyperalgesia in NMRs. Evidencesuggests that there is a difference in NMR TrkA ordownstream signaling that underlies the lack ofsensitization and these mechanisms are underinvestigation.

PLASTICITY-RELATED GENE-1SIGNAL TRANSDUCTION

Soriguera A1, Kieselmann O1, Singh B2, GrantynR2, Swiercz J3, Offermanns S3, Nitsch R1, andBräuer AU1

1. Institute for Cell Biology and Neurobiology, Center forAnatomy, Charité – Universitätsmedizin Berlin, Phillipstr. 12,10115 Berlin, 2. Institute for Physiology, Charité – Universi-tätsmedizin Berlin, Tucholskystr. 2, 10117 Berlin, Germany, 3.Institute of Pharmacology, University of Heidelberg, ImNeuenheimer Feld 366, 69120 Heidelberg, Germany

Lysophosphatidate (LPA) is involved in controllingcell signaling including the regulation of cell division,death and movement. In vivo concentration of LPAin brain tissue ranges is measured in µM. Our analysesof LPA-effects on neurons show that LPA inducesvesicle release on a subtype of synapses. LPA activatesat least five G-protein-coupled receptors (LPA1-5).Each receptor can couple with multiple types of Gproteins (G12/13, Gi/o, Gq/11, Gs) to activate a range ofdownstream pathways. We found that LPA induceseffects on neurons by coupling to the LPA2 receptor,which leads to an intracellular calcium increase.Extracellular LPA levels are controlled by a variety ofactors, including enzymes, namely three lipidphosphates phosphatases (LPPs), which degrade LPAto mono-acyl-glycerol and thus also regulate manyaspects of signaling transductions. We identified aset of five brain-specifically expressed membraneproteins, which define a subclass of the LPP-superfamily, the plasticity related genes (PRGs), which,in the case of PRG-1, attenuate LPA-induced effectson synapses. Further, we were able to identify thatPRG-1 interacts intracellularly with regulators of theRas-Rac signaling pathway depending on the LPAlevel extracellular. This protein-protein interactioncontrols N-Ras activity. Ras proteins are known to beinvolved in the growth and development of tumor.Interestingly, PRG-1 expression was found to beelevated in human prostate cancer tissue.This study is supported by DFG (BR 2345/1-1)

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ANALYSES OF PRG-1/RAS GRF-2INTERACTION AND SIGNALINGEFFECTS

Soriguera, A1; Swiercz, JM2; Offermanns, S2;Nitsch, R1; Bräuer, A.U.1

1PRG Research Group, Center for Cell Biology andNeurobiology, Charite-Universitätsmedizin Berlin, Philippstr.12, 10115 Berlin, Germany, 2Institute of Pharmacology,University of Heidelberg, Im Neuenheimer Feld 366, 69120Heidelberg, Germany

Plasticity-related gene-1 (PRG-1) was the first memberof the plasticity-related gene family (PRG-1-5) to beidentified. PRGs belong to the lipid phosphatephosphatases (LPP) superfamily whose members havean extracellular ectoenzymatic activity, which is ableto dephosphorylate lysophosphatidic acid (LPA) intoits inactive monomers. LPP-superfamily members arewidely expressed, but PRG-1 is brain-specific; PRG-1 expression in vivo increases after birth, is stilldetectable in adult mouse brain and is upregulatedafter brain lesion. Interestingly, PRG-1 has a particularlylarge intracellular C-terminus (400 amino acids). Toidentify the pathway involved in PRG-1, a yeast two-hybrid screening was performed. One of the putativeinteraction partners found was Ras-specific exchangefactor 2 (Ras GRF-2). Ras GRF-2 belongs to a familyof calcium/calmodulin-regulated guanine nucleotideexchange factors that activates Ras proteins. We couldconfirm the following: first, expression of PRG-1and Ras GRF-2 during brain development; second,colocalization of PRG-1 and Ras GRF-2 in primaryneurons; third, the interaction between both proteinsafter overexpression in mammalian cells, as well asendogenously in primary neurons using co-immunoprecipitation assays; Fourth, modification ofPRG-1/Ras GRF-2 interaction after extracellularinduction using LPA; and fifth, the direct effect ofPRG-1/Ras GRF-2 interaction on N-Ras inactivation.In summary, the results lead us to speculate a putativerole for PRG-1 as a Ras-cascade controller. Furtherstudies are being conducted to confirm this, not onlyto map the interaction (using several PRG-1 C-terminus-deleted mutants), but also to understand itssignaling.This project is supported by NaFöGs and DFG(BR2345/1-1)

OPIOID WITHDRAWAL INCREASESTRPV1 ACTIVITY IN A PKADEPENDENT MANNER

Viola Spahn, Christian ZöllnerCharité, CBF, Klinik für Anästhesiologie und operativeIntensivmedizin

Vanilloid receptor type 1 (TRPV1) is a ligand-gatedion channel expressed on sensory nerves thatresponds to noxious heat, protons, and chemicalstimuli such as capsaicin. TRPV1 plays a critical rolein the development of tissue injury, inflammation or

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nerve lesions. Opioids such as morphine have beenused widely for the treatment of many types of acuteand chronic pain. Application of morphine leads toa dissociation of G-proteins and causes a reducedactivity of adenylylcyclases (AC), resulting in a loweramount of cAMP. However, opioid withdrawalfollowing chronic activation of the µ opioid receptorinduces AC superactivation and subsequently anincrease in cAMP and Protein Kinase A (PKA) activity.In the current project we investigated wether anincrease in cAMP during opioid withdrawal increasesthe activity of TRPV1. In whole cell patch clamp andcalcium imaging experiments opioids significantlyincrease capsaicin induced TRPV1 activity in analaxone and pertussis toxin sensitive manner. Therole of different PKA phosphorylation sites at TRPV1was investigated using site-directed mutagenesis. Insummery, our results demonstrate that opioidwithdrawal can increase the activity of TRPV1. Theseobservations show a new mechanism underlyinghyperalgesia during opioid withdrawal.

INTERFERON-ß REVERSIBLYATTENUATES Ih IN ADULTNEOCOR-TICAL PYRAMIDALNEURONS IN VITRO

Konstantin Stadler, Claudia Bierwirth, Ulf StraussCharité Universitätsmedizin Berlin, Center for Anatomy,Institute of Cell Biology and Neurobiology

The cytokine IFN-ß modulates neuronal function byincreasing the excitability of neurons: it reversiblyinfluenced the subthreshold membrane response byraising the membrane resistance RM 2.5-fold and themembrane time constant t1.7-fold dose-dependently.The effect required permanent exposure to IFN-ßand was reduced in magnitude if the extracellular K+

was lowered. However, the membrane response toIFN- ß in the subthreshold range was prevented byZD7288 (a specific blocker of Ih) but not by Ni2+,carbachol, or bicuculline, pointing to a dependenceon an intact Ih. Consequently we directly showed byin vitro whole cell patch clamp recordings of layer Vpyramidal neurons in the somatosensory cortex ofadult rats that IFN-ß markedly and reversibly reducedthe current carried by hyperpolarization-activated cyclicnucleotide gated (HCN) channels, namely the slow Ihand the instantaneous Iinst. In case of Ih, IFN-ßappeared to predominantly affect the fastest currentcomponent as indicated by a concomitant 1.2-foldincrease of the first but not the second time constantof activation. All IFN-ß effects were dose dependentwith an IC50 of ~900 IU. Preliminary data point to aType 1 IFN-α/ß receptor mediated effect becauseblockade of the IFN1-receptor induced JAK1/Tyk2activation by JAK1 inhibitor prevented IFN-ß effectsalmost completely. On the contrary a preferentialblockade of JAK2 by AG490 did not interfere withthe IFN-ß induced Ih reduction. The data suggest thatIFN-ß can directly influence the membrane properties

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of layer V neocortical neurons by receptor mediatedmodulation of HCN channel activity. This action mayunderlie some of the effects of IFN-ß on brainfunction.

THE CONSOLIDATION OF ANEXTINCTION MEMORY DEPENDSON THE MAGNITUDE OF THE PRE-DICTION ERROR DURING MEMORYRETRIEVAL

Nicola Stollhoff & Dorothea Eisenhardt*Free University of Berlin, Institute of Biology, Neurobiology,Königin-Luise-Strasse 28/30, 19163 BerlinIn classical conditioning an animal learns that aprevious neutral stimulus (conditioned stimulus, CS)acts as a predictor for the appearance of abiologically significant stimulus (unconditionedstimulus, US). After an association has formedanimals display the conditioned response (CR) inanticipation of the US. Retrieving a consolidatedmemory about a CS-US association with anunreinforced CS-presentation results in twocontrasting memories. One is formed about the factthat the CS is no longer predicted by the US. Thismemory is termed extinction memory. The second isformed about the previously learned CS-USassociation, a process termed reconsolidation. Themechanisms underlying these consolidationprocesses after retrieval are still unclear. One criticalfactor for the induction of one or the otherconsolidation process is the intensity of the training.According to the Rescorla-Wagner-Model theassociative strength of a CS increases with everytraining trial until it reaches a maximum. Thus, theassociative strength of the CS appears to be criticalfor memory consolidation after retrieval. In this study,we tested this prediction in an pavlovian, appetitivelearning paradigm in the honeybee (Apis mellifera).We varied the length of US presentation, which isproposed to be directly related to the associativestrength. Associative strength is thought to be reflectedduring acquisition by its effects on the animal’s CRs.In the present study US length, showed no effect onthe animals CRs during acquisition. Moreover, whenbees trained with different US duration were exposedto CS presentations 24 h later no differences in theirCRs were observed. However, a consolidationblocker applied prior to the presentation of CS-onlytrials revealed that the duration of the last USpresentation during training is critical for aconsolidation process to occur after memoryretrieval. We conclude from this that it is the magnitudeof the prediction error during memory retrieval thataffects memory consolidation after retrieval.

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98 ANALYSIS OF PHOSPHORYLATIONTARGETS OF THE CGKI IN DEVEL-OPING DORSAL ROOT GANGLIAWHICH ARE IMPORTANT FORAXON BIFURCATION IN THESPINAL CORD

Agne Stonkute, Hannes Schmidt, Fritz G. RathjenMax-Delbrück-Center for Molecular Medicine, Berlin

Our lab showed that cGMP signaling via cGMPdependent protein kinase I (cGKI) is important inaxonal pathfinding and connectivity of sensoryneurons in vivo. Sensory axons bifurcate upon arrivalat the dorsal root entry zone (DREZ) of the spinalcord and grow further in both rostral and caudaldirections. However, sensory axons of mice lackingcGKI do not bifurcate, they turn instead and grow ineither caudal or rostral direction. These initial studiesraised the question which other components are partof the cGMP signaling cascade in sensory axons.PCR-screen of guanylyl cyclase expression carriedout in our lab indicated that natriuretic peptide receptor2 (Npr2) might be responsible for cGMP productionin dorsal root ganglia. When we studied afferentsensory projections in embryonic mice which lackfunctional Npr2 we observed the same axonalbifurcation errors as in cGKI knock-out mice. Ourdata suggest that cGMP signaling via Npr2 andcGKI is important for axon bifurcation at the DREZ.However, downstream phosphorylation targets ofcGKI involved in axon bifurcation remain to beidentified. We are searching for downstreamcomponents of the cGMP signaling cascade insensory axons by analysing mice deficient forestablished phosphorylation substrates of cGKI. Inaddition, we screen for novel phosphorylation targetsof cGKI using an antibody recognizing aphosphorylation consensus motif of cGKI.Experiments carried out so far let us exclude Menaand VASP proteins as candidate-proteins that couldplay a role in axon bifurcation. Western blots with thephospho-sequence specific antibody revealed severalproteins that become phosphorylated uponstimulation of cGKI in dorsal root ganglia or in a cellline derived from dorsal root ganglia. Currently wefocus on two components to enrich these for massspectrometry analysis.

PERINATAL HYPERPOLARIZA-TION-ACTIVATED CHANNEL SUB-TYPE REARRANGEMENT IN NEO-CORTICAL PYRAMIDAL NEURONS

Ulf Strauss, Nini Rocha und Anja U. BräuerInstitute for Cell Biology & Neurobiology, Center for Anatomy,Charité–Universitätsmedizin Berlin, 10115 Berlin, Germany

HCN channels - that conduct the hyperpolarizationactivated current Ih - play a paramount role in stabilizingresting membrane potential and controlling cell

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excitability in adulthood and during postnataldevelopment. We have discovered profound changesin HCN subunit expression around the time of birthwhich were partially transcriptional regulated. Theearly, strong expression of the ‚slow‘ subunits HCN3and HCN4 with a rapid decline postnatally appearsto be particularly important, shedding light on theirrole in cortical development. In contrast, HCN1 andHCN2 expeditiously increased postnatally. The distinctpattern of HCN subunit expression was reflected in Ihproperties which were changed in two kineticallydistinct manners. Firstly, a rapid change characterizedby a shift in voltage sensitivity to hyperpolarized valuesand by an accelerated deactivation occurred withinpostnatal day 1. Secondly, an 7-fold increase incurrent density accompanied by a diminution ofactivation kinetics and a shift in reversal potentialemerged in about 35 postnatal days. These findingspoint to a new role for HCN3 and adds evidence tothe suspected impact of HCN4 in neuronaldevelopment.

PAIN ATTENUATION IN TETHERED-TOXIN TRANSGENIC MICE DUE TOREDUCED EXCITABILITY OFSENSORY NEURONS

Annika Stürzebecher1, Jing Hu2, Gary R. Lewin2,Inés Ibañez-Tallon1

1 Molecular Neurobiology, Max-Delbrück-Centrum, Germany,2 Molecular Physiology of Somatic Sensation, Max-Delbrück-Centrum, Germany

Toxins derived from venomous animals have beenwidely employed in neuroscience research becauseof their ability to modulate specific ion channels.Our group has developed a new strategy usingpeptide toxins that are tethered to the membrane viaa GPI anchor and retain their specific action on ionchannel subtypes while acting in a cell-autonomousmanner. Since alterations in the function of voltagegated sodium channels (VGSCs) lead tohyperexcitability that causes chronic pain, we wantedto use this strategy to specifically manipulate thesechannels in vivo. We generated transgenic mice usingthe bacterial artificial chromosome (BAC) of theNav1.8 VGSC to drive expression of the MrVIAconotoxin. This toxin is a potent blocker of thistetrodoxin resistant (TTX-R) channel, which plays amajor role in nociception. A significant reduction ofVGSC currents in nociceptive neurons was observedwhile mechanoreceptors where not affected,demonstrating the cell subtype specificity of thisapproach. This block was restricted to TTX-R currentsand not compensated by upregulation of TTX-Scurrents as was observed in Nav1.8 knockout mice(Akopian et al). The Nav1.8 gene is predominantlyexpressed in non-peptidergic nociceptors (IB4+) andconsistent with this we observed an enhanced blockin this cell subpopulation. Behavioral studies revealeda remarkable lower sensitivity to noxious cold stimuli

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in the transgenic toxin mice. Thus these studiesprovide the first proof of function of the BACtransgenic tethered toxin approach in mammals andits suitability for developing new therapeutic mousemodels for pain research.(Supported by the DFG SFB 665)

ROLE OF PRG-1 IN HIPPOCAMPALEXCITABILITY

Trimbuch T.* 1, Beed P.* 2, Vogt J.* 1, NinnemannO.1, Schuchmann S.2, Schuelke M.2, BaumgartJ.1, Streu N.1, Geist B.1, Schlueter L.1, MeierN.2, Brunk I.4, Ahnert-Hilger G.4, Birchmeier C.3,Sendtner M.5, Braeuer A.1, Schmitz D.** 2 &Nitsch R.** 1 *These authors contribute equallyas first author, **These authors contributeequally to this work.1Charite, Institute of Cell- and Neurobiology, Berlin, Germany2Neuroscience Research Center (NWFZ), Berlin, Germany3Max-Delbrück-Center of Molecular Medicine (MDC),Berlin, Germany 4Charite, Institute of IntegrativeNeuroanatomy, Berlin, Germany; 5Institute of ClinicalNeurobiology, Würzburg, Germany

The information transmission at synapses is essentialfor neuronal processing in the nervous system.Abnormal excitation can lead to seizures in form ofepilepsy. We identified PRG-1, a member of the LipidPhosphate Phosphatase (LPP) superfamily, as a criticalmediator of excitation at glutamatergic synapses.PRG-1 is brain specific, and is expressed exclusivelyin glutamatergic neurons and not in glial cells. Inheterozygous breeding around 50% of PRG-1 nullmice die before P21 due to epileptic seizures. Weconfirmed this phenotype by in-vivo EEG recordingsof PRG-1 deficient mice which showed tonic-clonicseizures starting at P20. Field recordings in areaCA1 of hippocampus slices showed significantlyincreased excitability in PRG-1 deficient mice andheterozygous mice. In single cell recordings ofpyramidal neurons of the CA1 area, the frequencyof miniature EPSCs was significantly increased in theknock-out mouse at P21. However, the intrinsicproperties like action potential amplitude or restingmembrane potential of CA1 pyramidal neuronsshowed no differences between PRG1 deficient andwild type cells. Expression of postsynaptic receptorsand vesicular GABA or Glutamate transporters wasnot altered in the KO-Mice. In adult KO-mice typicalanatomical alterations such as mossy fiber sproutingand hippocampal sclerosis caused by epilepsy wereobserved. Thus, our findings reveal a novelmechanism that exerts important modulatory controlof glutamatergic transmission and hippocampalexcitability.

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102 THE INVOLVEMENT OF LIPIDPHOSPHATE PHOSPHATASES INCORTICOGENESIS

Velmans T., Gutsch R., Baumgart J., Nitsch R.,Bräuer AU.PRG Research Group, Institute for Cell Biology andNeurobiology, Center for Anatomy, Charité –Universitätsmedizin, 10115 Berlin, Germany

Lipid phosphate phosphatases (LPP) are integralmembrane proteins, which comprise sixtransmembrane domains. To date, three LPPs (LPP-1–3) and a splice variant (LPP-1a) have beenidentified. They are known to act as ectoenzymes,able to dephosphorylate and thereby control the levelsof extracellular phospholipids such aslysophosphatidic acid (LPA) and phosphatidic acid(PA). LPA is an extracellular lipid mediator with a widevariety of biological actions, including, in particular,induction of cell proliferation, migration and survival.It is known that the overexpression of LPP-1 shapesthe LPA-induced migration of fibroblasts in wound-healing assays in vitro. However, their expression,distribution and function in the brain remain unclear.In this study we were able to show by means of realtime PCR that LPP-1 mRNA is only weakly expressedin the neocortex, whereas LPP-1a expression isapproximately ten times stronger. Both genes areexpressed throughout embryonic and postnataldevelopment. We created an RNAi construct thatspecifically downregulates both splice variants. Invivo analysis of LPP-1 and LPP-1a knock down duringdevelopment by in utero electroporation showed thatLPP-1 and/or LPP-1a play an important role incorticogenesis. Cortical neurons that lack LPP-1 andLPP-1a expression are no longer able to migrate totheir proper layer. Further analysis of electroporatedneurons also showed possible alterations in dendritictree morphology. Our data provide evidence tosuggest that the expression level of lipid modulatorssuch as LPP-1 and LPP-1a and their control of thebioactive LPA-levels are important for neuronalmigration, cortical layer formation and perhapsdifferentiation in early embryonic neocortexdevelopment.

LOWER MOTOR NEURON LOSS:MULTIPLE SCLEROSIS AS - ANEURODEGENERATIVE DISEASE?

Vogt, J.1*; Paul, F.2*; Aktas, O.2*; Müller-Wielsch,K2; Dörr, J2; Bharathi, BS1,2, Dörr, S2, Schmitz,C3, Raine, CS4, Tsokos, M5, Nitsch, R1$, Zipp, F2$

1Institute of Cell Biology and Neurobiology, Center forAnatomy, Charité, 2Cecilie-Vogt-Clinic for Neurology inHKBB, Charité and Max-Delbrueck-Center for MolecularMedicine, 3Department of Psychiatry & Neuropsycholog,University of Maastricht, The Netherlands, 4Department ofPathology, Albert Einstein College of Medicine, New York,U.S.A., 5Institut of Forensic Medicine, Charité; * equallycontributing first authors, $ equally contributing senior authors

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Classical textbooks characterize multiple sclerosis(MS) as a chronic inflammatory and demyelinatingdisease of the CNS, but neither neurodegenerationnor lower motor neuron loss are stated as typicalfeatures of MS. Nerve conduction studies showedsignificantly lower compound muscle action potentialsand a significantly lower number of motor neuronsin MS patients versus controls, suggesting that spinalmotor neurons were affected. To determine whetherneuronal cell loss occurs in neuroinflammation, weassessed absolute numbers of neurons using high-precision, design-based stereology in patients withMS, but also in experimental autoimmuneencephalomyelitis (EAE), the animal model of MS.Surprisingly, we found a substantial loss of lowermotor neurons in MS patients (54 + 18%), althoughthis was not observed to this extent in cortical neurons.Lower motor neuron loss was also found in differentEAE models (49 + 11% to 76 + 8%) but wasabolished in EAE induced with TRAIL -/- T cells. Ourstudy reveals damage to the lower motor neuron asa significant feature, and neurodegeneration as amajor hallmark of MS.

ACUTE ALBUMIN EXPOSUREEFFECTS ARE STIMULATIONFREQUENCY DEPENDENT ANDSUGGEST POTASSIUM BUFFERINGIMPAIRMENT

Voitcu R.N. (1), Ivens S. (1), Friedman A. (1,2) &Heinemann U. (1)

(1 )Charite Univ. Berlin, Berlin, Germany ; (2) Ben-Gurion Univ.of the Negev, Beer-Sheva, Israel

The majority of insults that potentially lead to thedevelopment of chronic secondary epilepsy manifestthrough a temporary loss of integrity of the bloodbrain barrier (BBB), and subsequent infiltration ofplasma-specific proteins into the cerebral spinal fluid.Recent results point to serum albumin as a maincause of astrocytic activation characterized by downregulation of Kir4.1 channels and changes inexpression of glutamate transporters. Modeling workpredicted that induction of epileptiform discharges isfacilitated due to alterations in potassium (K+)clearance when low frequency stimulation is used,while decline in glutamate transport would favorgeneration of epileptiform discharges if high frequencystimulation were used. We used horizontal slices totest for effects of albumin on neuronal activity whilerecording in somatosensory, temporal and entorhinalcortex. Acute albumin exposure led after a few hoursto the appearance of abnormal field potentialresponses in cortical layer IV and II, for layer VIstimulation, in all studied regions. The effects ofalbumin were measured in presence and absence of2mM glutamine. Spontaneous epileptiform eventsappeared only in the presence of glutamine inentorhinal cortex and temporal neocortex, wherealbumin is preferentially taken up during a generalized

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exposure. Additionally, repetitive stimulation withdifferent frequencies could induce epileptiform after-discharges. Low frequency stimulation was moresuccessful than high frequency stimulation. Thisresult is compatible with modeling work indicatingthat impairment of spatial K+ buffering and abnormalK+ accumulation is involved in generating abnormaldischarges after low frequency stimulation.Supported by Epicure and SFB TR3

THE ROLE OF THE THYROIDHORMONE-SPECIFIC TRANSPOR-TER MCT8 IN CNS DEVELOPMENT

Wirth, EK1); Roth, S1); Kinne, A1); Ambrugger,P2); Biebermann, H2); Grüters-Kieslich, A2);Schweizer, U1)

1) Institute for Experimental Endocrinology and NeuroscienceResearch Center, 2) Institute for Experimental PediatricEndocrinology, Charité - Universitätsmedizin BerlinThyroid hormones are essential for the properdevelopment of a variety of tissues, especially thenervous system. Their transport into target cells ismediated by thyroid hormone transporters like themonocarboxylate transporter 8. Mutations in this X-chromosomal gene in humans lead to a severephenotype with lack of mental development afterbirth, derangement of thyroid hormone levelsincluding high T3 and low T4, with no significantchanges in TSH. Interestingly, despite high T3 thepatients do not show tachycardia. Here we presentdata on the expression of MCT8 in various tissues inhuman and mouse. Despite the lack of the sameobvious phenotype in the MCT8 knock-out mouse,the transporter causes reduced anxiety-relatedbehaviour and hyperalgesia in these mice. Thyroidhormone transport is significantly down-regulated inMCT8-deficient primary cortical neurons. We couldfind an up-regulation of other thyroid hormonetransporters in these cells from KO mice which couldaccount for the incomplete loss of thyroid hormoneuptake in these cells.

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RGS PROTEIN SUPPRESSION OF GALPHA(O) PROTEIN-MEDIATEDALPHA-2A ADRENERGIC INHIBI-TION OF MOUSE HIPPOCAMPALCA3 EPILEPTIFORM ACTIVITY

Xu, K.; Goldenstein, B.; Nelson, B.; Luger, E.;Pribula, J., Wald, J.; Weinshenker,D.;Charbeneau, R.;Huang, X.; Neubig, T.; Doze,V.1Pharmacology, Physiology & Therapeutics, University ofNorth Dakota, Grand Forks, ND; 2Human Genetics, EmoryUniversity, Atlanta, GA; 3Pharmacology, University ofMichigan, Ann Arbor, MI

G-protein coupled α2 adrenergic receptor (AR)

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activation by epinephrine (EPI) inhibits epileptiformactivity in the mouse hippocampal CA3 region. Themechanism underlying this action is unclear. Thisstudy investigated which subtypes of α2ARs and G-proteins (Gαo or Gα1) were involved in this responseusing recordings of CA3 epileptiform bursts inmouse brain slices. First, we determined that thiseffect was mediated by the 2AAR subtype as theinhibitory action of EPI on burst frequency wasabolished in slices from α2AAR, but not α2CAR,knockout mice. Next, using transgenic mice with theG184S Gnai2 allele (knock-ins) which preventsinhibition by interruption of the G-protein alpha subunitbinding to regulators of G-protein signaling (RGS),we found enhanced α2AAR effects in hippocampalslices from mutant Gαo mice but not Gαι2 mice.These results indicate that the EPI-mediated inhibitionof mouse hippocampal CA3 epileptiform activity isthrough an α2AAR Gαo mediated pathway underinhibitory control by RGS proteins. This suggests arole for RGS inhibitors as a novel antiepileptic drugtherapy. Supported by American Physiological Society,ND EPSCoR EPS-0447679, NSF 0347259, NSF0639227, NIH P20RR0167141, NIH 5RO1DA17963 and NIH 5RO1GM039561.

PERIPHERAL AND CENTRALORGANIZATION OF THE LATERALLINE PATHWAY IN XENOPUSLAEVIS

Z. Zhivkov, C. Schuldt, F. Branoner and O.BehrendAquatic Bioacoustics Lab, Institute of Biology, HumboldtUniversity Berlin, GermanyHumboldt University Berlin,Institute of Biology, Head, Aquatic Bioacoustics Laboratory,Invalidenstr. 43, 10115 Berlin

Aquatic vertebrates like Xenopus make use of a lateralline (LL) system to detect water surface waves elicitedby prey or predator movements. In Xenopus, only afew neuroanatomical studies on the LL-pathway exist,and the assignment of CNS nuclei to different LL-processing tasks remains incomplete. In a first step,the spatial arrangement of primary afferents into theCNS from individual peripheral LL-organs wasinvestigated by a newly established double-labellingprocedure using different tracers (neurobiotin andHRP). In the CNS, a combined neurophysiologicaland neuroanatomical approach was used for labellingexperiments: responses of LL units were extracellularlyrecorded in different regions of the midbrain ofXenopus. Subsequently, neurobiotin wasiontophoretically applied to reconstruct recordingsites, and to track tracer transport. Injections wereapplied in the optic tectum (OT; 7 animals), as wellas the principal nucleus of torus semicircularis (TP;2 animals). In all animals and both injection sites,strong ipsilateral retrograde labelling of cell bodiesin three tegmental subdivisions (dorsal, ventral, and

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nucleus isthmi) was observed (NOT-Injection=25; NTP-

Injection=18; mean). In 5 of 9 frogs, significant ipsilateralretrograde transport was observed in the laminarnucleus of torus semicircularis after injection in theOT and the TP (NOT=19 (mean); NTP=15). Otherthan OT injections, both TP injections demonstratesignificant ascending input from decussating LL-fibrescoming from the lateral line nucleus of the medulla(NMED=10, and 31 respectively). Both the OT andthe TP receive descending fibres from diencephalicnuclei indicated by retrogradely filled cell bodies(NTP=15; NOT=9; mean). The results suggest thetegmentum and the laminar torus participate in LL-processing, and confirm that the TP is a mainprojection area of medullary LL-neurones.Descending projections from the diencephalon mightindicate efferent control from higher levels in the LL-hierarchy.

HYPERPHOSPHORYLATION OFTAU IN NPC-/- P301L-TAU+/+ MICE

S.Zonnur 1, J. Goetz 2, T.G.Ohm 11 Institute for Neuroanatomy, Charité, Berlin, Germany, 2 Brainand Mind Research Institute, University of Sydney, Sydney,Australia

Neurofibrillary Tangles (NFTs), intracellular depositsconsisting mostly of insoluble microtubule-associatedprotein tau, are a hallmark for a wide range ofneurodegenerative diseases including Alzheimer’sdisease, frontotemporal dementia with parkinsonismlinked to chromosome 17 (FTDP-17) and Niemann-Pick-disease type C (NPC). A number of animalmodels has been created to mimick these diseases.But while much has been learned by investigatingthese models, the specific mechanisms leading tothe formation of NFTs are still unclear. While NFTscan be found in P301L-tau-mice older than 3months, npc-mice do not develop NFTs. By creatinga new mouse model by crossing balb/c npc-micewith P301L-tau-mice we sought to find out if NPC-disease could increase or accelerate tau pathologyin mice posessing human tau with P301L-mutation.Comparing npc-/- P301L-tau+/+ with npc+/+P301L-tau+/+ mice, we found in npc-/- P301L-tau+/+ mice an increase of tau phosphorylated atsome epitopes (AT8, AT180), but an decrease oftau phosphorylated at the 12E8 epitope and noincrease of the amount of tau phosphorylated at theAT100 epitope or in the number of NFTs. Althoughtau phosphorylation is thought a necessaryprerequisite for NFT formation, we did not findmore NFTs in spite of tau hyperphosphorylation atsome epitopes. So further investigations are neededto understand the chain of events that lead fromhyperphosphorylated tau to NFTs formation.

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ROLE OF THE FOXP2 GENE IN PRO-LIFERATION AND NEUROGENESISIN THE VENTRICULAR ZONE OFZEBRA FINCHES, AN AREA DELI-VERING NEWLY BORN NEURONSTO THE SONG NUCLEI AREA X

Steffen SchulzFreie Universität Berlin, Institute of Biology, Department ofAnimal Behavior, Takustr. 6, D-15195 Berlin

So far it is known that FoxP2, a member of theforkhead box transcription factors, is involved inlearning and acquisition of speech and song inhumans and songbirds like zebra finches, respectively.In the male zebra finch it is, amongst others, expressedin the ventricular zone, the region where new neuronsarise, and in two song nuclei, HVC in the palliumand Area X in the striatum, whereto a part of thenewly born neurons of the ventricular zone migrateduring the sensorimotory learning phase. To test ifthe FoxP2 gene may have a main function inregulating neurogenesis and in predefining themorphologic structures of the newly born neurons, Iperform knock-down experiments in the ventricularzone via stereotactical injections of a self-madelentivirus, and analyse potential changes in the totalamount and in the structure of new cells. To makethe changes visible, I perform immunohistochemistrywith antibodies against GFP, which is expressed bythe virus, against BrdU, which is a thymidin-analogonthat is incorporated into the DNA of dividing cellsand which I apply one week after the virus injections,and against Hu, a general marker of neurons.

FOXP2 TARGET GENES IN AREA XOF ZEBRA FINCHES

Iris AdamFreie Universität Berlin, Institute of Biology, Department ofAnimal Behavior, Takustr. 6, D-15195 Berlin

Mutations of the transcription factor FoxP2 arecausing Developmental Verbal Dyspraxia (DVD), adisorder where the affected individuals show severeimpairments in the expression and reception ofspeech and language. Studies have shown that FoxP2is differentially expressed in a nucleus of the avianbasal ganglia, namely Area X, during the period wherethe bird learns its song. A knockdown of FoxP2 inArea X during that sensitive phase leads to theincomplete and inaccurate acquisition of the tutorsong. As FoxP2 is a transcription factor the displayedphenotype is likely due to the missregulation of itsdownstream target genes. Therefore the identificationand further investigation of those targets will lead toa better understanding of the role of FoxP2 inlearning. In my diploma thesis I am validating ChIP-on-Chip predicted FoxP2 targets by doing in situhybridizations on zebra finch brains of different ages,with and without FoxP2 knockdown. Targets that are

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differentially expressed in Area X and colocalize withFoxP2 will be further investigated in in vivo knockdownexperiments, that will allow us to enlighten the role ofFoxP2 and its target genes in auditory guided motorlearning.

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07Information on Berlin Neuroscience ProgramsInformation on Berlin Neuroscience ProgramsInformation on Berlin Neuroscience ProgramsInformation on Berlin Neuroscience ProgramsInformation on Berlin Neuroscience Programs

SFB 507 “Role of non-neuronal cells inSFB 507 “Role of non-neuronal cells inSFB 507 “Role of non-neuronal cells inSFB 507 “Role of non-neuronal cells inSFB 507 “Role of non-neuronal cells inneurological disorders”neurological disorders”neurological disorders”neurological disorders”neurological disorders”

The Sonderforschungsbereich 507 was funded from 1995 to 2007 and investigated therole of non-neuronal cells in CNS disease. In particular, the role of astrocytes, microglia,and endothelial cells in neurological diseases such as stroke, multiple sclerosis, meningitis,and epilepsy was studied. Systems-physiological, molecular, and cellular strategies wereutilized to understand the complex interaction of neurons and non-neuronal cells inmodels of neurological disorders. Special emphasis was put on clinical relevance, since itwas the ultimate goal of this collaborative effort, which briought together clinicaldepartments with basic research units, to develop new diagnostic and therapeutic tools.The SFB 507 was coordinated by Ulrich Dirnagl (‚Sprecher‘, Charité Exp. Neurology),Uwe Heinemann (Charité Physiology), Frauke Zipp (Charité Neuroimmunology), HelmutKettenmann (MDC), and Jens Dreier (Charité Neurology).

Projektbereich AA1 ‚Cortical spreading ischemia‘, Dreier/EinhäuplA5 Rekrutierung myeloider und lymphoider Zellen ins ZNS nach experimentellemSchlaganfall, Priller/DirnaglA9 Angiogenese und Vaskulogenese nach milder zerebraler Ischämie, EndresProjektbereich BB6 Zelluläre Schädigung der Blut-Hirn-Schranke - Ein Schlüsselmechanismus in derSchadenskaskade der bakteriellen Meningitis, Weber/BraunB11 Die Rolle des Netzwerkes nicht-neuronaler Zellen bei axonalem Auswachsen, Nitsch/Müller-RöverB14 Mechanismen der Immunzell-vermittelten Schädigung in der chronischen Entzündungdes Zentralnervensystems, Zipp/AktasB16 Die Rolle der Mikroglia bei postläsionalen Veränderungen in Schichten anterograderaxonaler Läsion, BechmannB18 Das Proteasom in Mikroglia und Astrozyten und seine Rolle bei Infektions- undEntzündungsprozessen im ZNS, Kloetzel/DahlmannProjektbereich CC3 Funktionen von Gliazellen während epileptogener Prozesse, Heinemann/KannC7 In situ Untersuchungen zu physiologischen Mechanismen der Mikrogliaaktivierungunter pathophysiologischen Bedingungen, Schilling/EderC10 Kommunikation von Mikrogliazellen mit Astrozyten und Neuronen, KettenmannC12 Die Bedeutung von Bluthirnschrankenstörungen für Dysfunktionen des cerebralenCortex, Friedman/Heinemann

Kontakt:Kontakt:Kontakt:Kontakt:Kontakt:Prof. Dr. Ulrich DirnaglSFB 507CharitéNeurologische KlinikSchumannstr. 20/2110098 BerlinTel.: +49 30 45056 0134Fax: +49 30 45056 0942EMail: ulrich.dirnagl@charite.de

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of the SFB 507Information on Berlin Neuroscience ProgramsInformation on Berlin Neuroscience ProgramsInformation on Berlin Neuroscience ProgramsInformation on Berlin Neuroscience ProgramsInformation on Berlin Neuroscience Programs

SFB 665 “Entwicklungsstörungen im NervensystemSFB 665 “Entwicklungsstörungen im NervensystemSFB 665 “Entwicklungsstörungen im NervensystemSFB 665 “Entwicklungsstörungen im NervensystemSFB 665 “Entwicklungsstörungen im Nervensystem“““““(„Developmental Disturbances in the Nervous System(„Developmental Disturbances in the Nervous System(„Developmental Disturbances in the Nervous System(„Developmental Disturbances in the Nervous System(„Developmental Disturbances in the Nervous System“)“)“)“)“)

Seit Juli 2005 fördert die Deutsche Forschungsgemeinschaft (DFG) denSonderforschungsbereich 665 »Developmental Disturbances in the Nervous System«, dervon der Charité geleitet wird. 15 Forscherteams aus der Charité – UniversitätsmedizinBerlin, der gemeinsamen Einrichtung der Freien Universität (FU), der Humboldt- Universitätzu Berlin (HU), dem Max-Delbrück-Centrum für Molekulare Medizin (MDC) und demInstitut für Biologie der FU, forschen zusammen nach Wegen, Entwicklungsstörungen desNervensystems aufzuklären.Wie das Nervensystem während der Entwicklung ausgebildet wird, ist ausschlaggebendfür seine spätere Funktion. Fortschritte in der Genetik und der Molekularbiologie in denletzten zwei Jahrzehnten haben es ermöglicht, Moleküle zu analysieren, welche dieEntwicklung des zentralen Nervensystems steuern, und genetische Veränderungen zuidentifizieren, die zu einer Störung dieses Prozesses führen. Wenn beispielsweise durcheine Mutationen kritische Zellfunktionen gestört sind, führt dies oft zu einer Kaskadeweiterer Probleme, die schließlich zu einer Anzahl klinischer Syndrome führen können,wie z.B. Schwerhörigkeit, Epilepsie oder Sprachstörungen.Wie neuronale Schaltungen gebildet und aufrechterhalten werden, ist jedoch bis jetzt nurteilweise aufgeklärt. Die Herausforderung für Grundlagenforscher und klinischeNeurowissenschaftler ist deshalb, das Wissen über molekulare Mechanismen, welchesdurch Tiermodelle gewonnen wurde, in das Verständnis von Entwicklungsstörungen beiPatienten zu integrieren. Langfristiges Ziel des SFB 665 ist es deshalb, Kausalzusam-menhänge zwischen Mutationen und neurologischen Phänotypen aufzuklären und dadurcheine Basis für zukünftige Verbesserungen therapeutischer Strategien zu schaffen. Der SFB665 stellt sich diesen Herausforderungen, indem er Grundlagenforscher und Klinikerzusammenbringt, um die Funktionen des Nervensystems auf zellulären, biochemischenoder physiologischen Ebenen zu untersuchen und die genetischen Ursachen vonEntwicklungsstörungen bei Patienten zu identifizieren.

Kontakt:Kontakt:Kontakt:Kontakt:Kontakt:Prof. Dr. Robert NitschSFB 665Charité - Universitätsmedizin BerlinCentrum für AnatomieInstitut für Zell- und NeurobiologieSchumannstr. 20/2110098 BerlinTel.: +49 30 450 528 072Fax : +49 30 450 528 902EMail: robert.nitsch@charite.de, sfb665@charite.dehttp://www.charite.de/sfb665

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SFB/TRR 43 “SFB/TRR 43 “SFB/TRR 43 “SFB/TRR 43 “SFB/TRR 43 “The Brain as a TThe Brain as a TThe Brain as a TThe Brain as a TThe Brain as a Target of Inflammatoryarget of Inflammatoryarget of Inflammatoryarget of Inflammatoryarget of InflammatoryPPPPProcesses"rocesses"rocesses"rocesses"rocesses"

Recent paradigm shifts in our understanding of pathologies of the central nervous system(CNS) call for elucidation of the underlying molecular processes. It has become evidentthat classical inflammatory disorders of the CNS such as multiple sclerosis and meningitistarget the neuroaxonal compartment, an aspect which has been neglected for over acentury. Moreover, evidence is growing for a fundamental role of both innate and adaptiveimmunity in pathologies which have not hitherto been regarded as inflammatory, such asstroke – both ischemic and hemorrhagic – and axonal/neuronal injury due to traumatic ordegenerative causes.In this SFB, researchers from Berlin and Göttingen have come together to take up thechallenges of this emerging field, by combining the efforts of clinicians and basic scientists,neuroimmunologists and neurobiologists. The key questions we seek to answer are asfollows:• Under what circumstances and by what mechanisms do immune cells enter the CNS andinteract with, or even attack, local neural cells?• Does the involvement of the immune system in different pathologies result in additionaldamage or does it, in specific situations, promote repair, and if so, what are the molecularprocesses of immune-mediated damage and repair within the CNS?Two features of the interaction of the immune system with the nervous system form theorganizational basis of our SFB: firstly, the rapid innate immune (i.e. microglial) responses,with microglia being part of both the immune and the nervous system (project area A);secondly, adaptive immune (i.e. T cell) responses, since T cells infiltrate and traffic throughthe CNS in various CNS diseases (project area B). It is our hypothesis that the crosstalk ofthe nervous and immune systems is a common mechanism in various pathologicalconditions, and as such a suitable target for therapeutic interventions.

Speaker: Speaker: Speaker: Speaker: Speaker: Prof. Dr. Frauke Zipp

Contact:Contact:Contact:Contact:Contact:Alistair NoonCecilie-Vogt-Klinik für Neurologie im HKBB BerlinCharité Universitätsmedizin BerlinCharitéplatz 110117 BerlinTel: +49 30 450 539028EMail: alistair.noon@charite.dewww.charite.de/sfb-trr43

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GRK 429 “Doctoral PGRK 429 “Doctoral PGRK 429 “Doctoral PGRK 429 “Doctoral PGRK 429 “Doctoral Program onrogram onrogram onrogram onrogram onNeuropsychiatry and PNeuropsychiatry and PNeuropsychiatry and PNeuropsychiatry and PNeuropsychiatry and Psychology of Aging”sychology of Aging”sychology of Aging”sychology of Aging”sychology of Aging”

Central Themes of the Program:It is generally agreed that, in order to understand the many aspects of old age and aging,it is important to strive for a transdisciplinary perspective and systematic integration. Tothis end, two main goals of the Research Training Program on the neuropsychiatry andpsychology of aging are:

- To integrate neuropsychiatric and psychological questions in research on aging- To focus on issues of healthy and pathological aging.

In addition, the program seeks to integrate gerontological research and themes withstudies and theoretical frameworks from health psychology.

Several topics serve as a forum for these integrative efforts. These include: brain agingand plasticity, pathological versus normal aging, the gain-loss dynamics of aging, thepotential and limits of old age, cognition and sleep in elderly persons, and the nature ofresiliency in old age.

One of the main research project currently in progress is called, “Berlin stays fit”. Itexamines the effect of cognitively versus physically stimulating activities on the cognitivestatus of healthy elderly women.

Speaker: Speaker: Speaker: Speaker: Speaker: Prof. Dr. Isabella Heuser

Contact:Contact:Contact:Contact:Contact:Hu-Ping ChenDepartment of PsychiatryCharitéCampus Benjamin FranklinEschenallee 314050 BerlinTel: +49 30 84458701E-mail: hu-ping.chen@charite.dewww.charite.de/age

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GRK 1258 „Der Einfluss von Entzündungen auf dieGRK 1258 „Der Einfluss von Entzündungen auf dieGRK 1258 „Der Einfluss von Entzündungen auf dieGRK 1258 „Der Einfluss von Entzündungen auf dieGRK 1258 „Der Einfluss von Entzündungen auf dieFFFFFunktion des Nervensystemsunktion des Nervensystemsunktion des Nervensystemsunktion des Nervensystemsunktion des Nervensystems“““““

(„(„(„(„(„The impact of inflammation on nervous system functionThe impact of inflammation on nervous system functionThe impact of inflammation on nervous system functionThe impact of inflammation on nervous system functionThe impact of inflammation on nervous system function“)“)“)“)“)

There is increasing evidence that immunological processes are involved not only in theclassical inflammatory disorders of the nervous system but also in primarily non-inflammatory injuries, such as trauma and ischemia, or even in functions of the nervoussystem, such as pain transmission. In all of these conditions or disorders, immune cellsinteract with cells of the nervous system. Although the initiating events differ considerably,we hypothesize common pathways in the crosstalk between immune and nervous system.The faculty of this graduate program studies this crosstalk by combining modern methodsof molecular and cellular biology with imaging techniques (two photon microscopy, near-infrared fluorescence, and magnetic resonance imaging). We employ in vivo and in vitroapproaches including animal models of neuroinflammation, ischemia, and arthritis, and inparallel we offer students experience in outpatient clinics and ward-rounds.

Our aim is to elucidate the influence of both proinflammatory and regulatory immunecells, via contact or soluble mediators, on brain cells, namely astrocytes, microglial cellsand neurons. We will analyse the immune-triggered responses of brain cells and studytheir impact on function, pathologic processes, damage cascades, and regeneration innervous tissue. Studying the underlying mechanisms of these processes will be a challengefor motivated young students at the same time as providing them with an excellentopportunity to learn different approaches. The graduate program is integrated into theHumboldt University’s International Masters - MD/PhD Program Medical Neurosciences.

Speaker: Speaker: Speaker: Speaker: Speaker: Prof. Dr. Helmut Kettenmann, Prof. Dr. Frauke Zipp

Contact:Contact:Contact:Contact:Contact:Stefanie KorthalsMax Delbrück Center for Molecular MedicineOffice Research Training Group ‚Neuroinflammation’Robert-Rössle-Str. 1013122 BerlinTel.: +49 30 9406 3127Fax: +49 30 9406 3819EMail: korthals@mdc-berlin.dehttp://neuroinflammation.glia.mdc-berlin.de/

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GRK 1123 “Zelluläre Mechanismen von Lernen undGRK 1123 “Zelluläre Mechanismen von Lernen undGRK 1123 “Zelluläre Mechanismen von Lernen undGRK 1123 “Zelluläre Mechanismen von Lernen undGRK 1123 “Zelluläre Mechanismen von Lernen undGedächtniskonsolidierung in der hippokampalenGedächtniskonsolidierung in der hippokampalenGedächtniskonsolidierung in der hippokampalenGedächtniskonsolidierung in der hippokampalenGedächtniskonsolidierung in der hippokampalen

FFFFFormationormationormationormationormation”””””

Das Graduiertenkolleg bietet die Möglichkeit, zelluläre Mechanismen von Lernen undSpeicherung von Informationen im Gedächtnis sowie der Gedächtniskonsolidierung zuuntersuchen. Ein Verständnis dieser Vorgänge ist von herausragender bio-medizinischerBedeutung, da sie zum einen die Fähigkeit eines Organismus bestimmen, sich unabhängigvon genetisch determinierten Verhaltensweisen an neue Umweltbedingungen anzupassen:das explizite Gedächtnis bestimmt entscheidend das menschliche Verhalten und istVorrausetzung für die eigene Individualität. Zum anderen sind die zugrunde liegendenMechanismen störanfällig und damit in verschiedene neurologische und psychiatrischeKrankheiten involviert. Hierzu zählen z. B. die Temporallappenepilepsie und dieAlzheimersche Erkrankung. Zu den am intensivsten untersuchten zellulären Modellen fürLernen und Gedächtnis zählen die Langzeitpotenzierung (LTP) und Langzeitdepression(LTD). Allerdings sind noch viele der beteiligten prä- und postsynaptischen Mechanismenweitgehend unverstanden. Um langanhaltend Information zu speichern undGedächtnisinhalte zu konsolidieren, bedarf es der Geninduktion und der Translationspezifischer Proteine, die die zugrunde liegenden Veränderungen in neuronalen Netzwerkenermöglichen. Auf zellulärer und neuronaler Netzwerkebene könnten an derGedächtniskonsolidierung die Ausbildung von sharp wave ripple Komplexen, dieFormierung von Frequenzgedächtnis und eine niederfrequent induzierte heterosynaptischeLTP beteiligt sein. Zusätzlich könnten gespeicherte Informationen während desTraumschlafes wieder aktiviert werden, wobei die neuronale Aktivität von Theta- undGammaoszillationen überlagert ist. Hierdurch können Veränderungen synaptischerKopplung weiter verstärkt werden und schließlich aus dem Hippokampus in andereHirnareale übertragen werden. Jeder der 11 am Graduiertenkolleg beteiligten Tutorenwird zu diesen Problemen spezifische Expertise beitragen. Elektrophysiologische,zellbiologische, genetische und verhaltensphysiologische Methoden sowie Modellierungvon Netzwerkeigenschaften bieten den Studenten des Graduiertenkollegs die Möglichkeit,zu diesem aufregenden Gebiet der Neurowissenschaften beizutragen mit hervorragendenChancen, eine exzellente Ausbildung in modernen neurobiologischen Methoden zuerhalten.

Sprecher: Sprecher: Sprecher: Sprecher: Sprecher: Prof. Dr. Dietmar Kuhl

Kontakt:Kontakt:Kontakt:Kontakt:Kontakt:Barbara Neuhoff M.A.Koordinatorin GRK 1123Institut für NeurophysiologieTucholskystr. 210117 BerlinTel.: +49 30 450-528112Fax: +49 30 450-528962EMail: barbara.neuhoff@charite.dewww.charite.de/ch/physio/neuro/grk1123

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Berlin School of Mind and BrainBerlin School of Mind and BrainBerlin School of Mind and BrainBerlin School of Mind and BrainBerlin School of Mind and Brain

The focus of the school is on the interface of humanities and behavioral sciences(philosophy, social sciences, linguistics, behavioral and cognitive psychology) withneurosciences (neurophysiology, psychiatry, computational neuroscience, neurobiology).Research concentrates on the following topics: “conscious and unconscious perception”,“decision-making”, “language”, “brain plasticity and lifespan ontogeny” and “mentaldisorders and brain dysfunction”.During the first year of their dissertation Mind and Brain doctoral students take part in tenweeks of research-related instruction:: Neurophysiology, Systems and CognitiveNeuroscience, Neuroscience Methods, Behavioral Research Methods and ExperimentalDesign, Basic Philosophical Concepts and Introduction to the Philosophy of Mind,Computational Neuroscience, Cognitive Science, Clinical Neuroscience, Advanced Issuesin Philosophy of Mind and Practical Philosophy, Language and the Brain (20 CP).Generally, students work closely with their supervisors on designing a curriculum thatcaters to their specific needs and interests and fosters their development in becomingwell-grounded mind and brain researchers.During the second and the third year of the doctoral program the focus is on the writingand completion of the dissertation.Throughout the three-year program students attend an international lecture series, journaland methods clubs, poster presentations, conferences and workshops (5 CP). They areobliged to take a number of scientific soft skills courses, such as presentation skills, grant-application writing, scientific writing (5 CP), and are offered dissertation coaching,mentoring, and career advice.The school’s faculty comprises researchers of Humboldt-Universität, Freie Universität,Technische Universität, Max Planck Institute for Human Development (all based in Berlin),Universität Potsdam, Universität Magdeburg, Max Planck Institute for Human Cognitiveand Brain Sciences, Leipzig.

Speaker: Speaker: Speaker: Speaker: Speaker: Prof. Dr. Michael Pauen

Contact:Contact:Contact:Contact:Contact:Humboldt-Universität zu BerlinUnter den Linden 610117 Berlinwww.mind-and-brain.de

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Berlin NeuroImaging Center (BNIC)Berlin NeuroImaging Center (BNIC)Berlin NeuroImaging Center (BNIC)Berlin NeuroImaging Center (BNIC)Berlin NeuroImaging Center (BNIC)

Das Berlin NeuroImaging Center ist ein Berlin-weites Verbundprojekt, das die FU und diePTB einschließt und an der Charité koordiniert wird. Die übergeordneten Themen desBerlin Neuroimaging Center ergeben sich aus den langjährigen wissenschaftlichenSchwerpunkten der beteiligten neurowissenschaftlichen Institutionen in Berlin. Es sinddies die Erforschung zerebrovaskulärer Erkrankungen, insbesondere des Schlaganfallsund damit eng verknüpft das Forschungsgebiet der neurovaskulären Kopplung.Zerebrovaskuläre Erkrankungen stellen eine große medizinische Herausforderung dar.Zwar bedeuten neuere Verbesserungen im Bereich bildgebender Verfahren einen wichtigenDurchbruch für ihr besseres Management, allerdings besteht weiterhin ein unzureichendesVerständnis der physiologischen und pathophysiologischen Mechanismen beim(individuellen) Patienten mit Schlaganfall. Darüber hinaus können die zur Zeit eingesetztenbildgebenden Techniken nicht direkt am Patientenbett angewendet werden, so dass ihreBedeutung hinsichtlich akuter Therapiemöglichkeiten in der Klinik eingeschränkt ist. Umdiese methodischen Limitierungen zu überwinden, beabsichtigen wir mit dem hiervorgeschlagenen Zentrum Erkenntnisse zusammenzuführen, die in einem multimodalenAnsatz mit unterschiedlichen bildgebenden Verfahren gewonnen wurden. Damit sollengrundlegende physiologische und pathophysiologische Zusammenhänge aufgeklärt undneue Technologien zur Anwendung am Patientenbett entwickelt werden.

Kontakt:Kontakt:Kontakt:Kontakt:Kontakt:

Berlin NeuroImaging CenterKlinik und Poliklinik für NeurologieCharité - Universitätsmedizin BerlinCampus Charité MitteCharitéplatz 110117 BerlinTel.: +49 30 450 560142Fax: +49 30 450 560952EMail: julia.schlueter@charite.dehttp://www.berlin-neuroimaging-center.de/

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Klinische FKlinische FKlinische FKlinische FKlinische Forschergruppeorschergruppeorschergruppeorschergruppeorschergruppe“Molecular Mechanisms of Opioid Analgesia in“Molecular Mechanisms of Opioid Analgesia in“Molecular Mechanisms of Opioid Analgesia in“Molecular Mechanisms of Opioid Analgesia in“Molecular Mechanisms of Opioid Analgesia in

Inflammatory PInflammatory PInflammatory PInflammatory PInflammatory Painainainainain”””””

Our group is interested in mechanisms of inflammatory pain and its inhibition by opioidsoutside the CNS. Opioids remain the major therapy for severe acute (e.g. postoperative)and chronic (e.g. cancer-related) pain. However, serious side effects such as sedation,respiratory depression, dependence and addiction resulting from the opioid action in theCNS limit their therapeutic applications. Studies of our and other groups have providedevidence on effective analgesia, free of CNS adverse effects, after activation of opioidreceptors on peripheral sensory nerves. This can be achieved by opioid application directlyinto peripheral injured tissues or by administration of opioids with limited CNS access.Moreover, endogenous opioid peptides, such as endorphin, are produced by immunecells accumulating in inflamed tissues. Activation of such opioid-cells by stressful stimuli,application of cortictoropin-releasing factor, adrenergic drugs or chemokines liberatesopioids. Currently the following topics are being investigated:- Transcriptional regulation of the endorphin precursor proopiomelanocortin inlymphocytes: influence of cytokines and the JAK/STAT pathway.- Subcellular pathways of opioid peptide synthesis, processing and release from leukocytes.- Analgesic and antiinflammatory actions of leukocyte-derived opioids by stimulating theirsecretion and by inhibiting their enzymatic degradation in animal models and patients witharthritis.- Opioid peptides and receptors in leukocytes and the control of neuropathic pain.- Opioid receptor coupling with potassium channels in peripheral sensory neurons.- Perineurial barrier function and effective opioid analgesia.- Kinin receptors in the generation of pain and its inhibition by interactions with peripheralopioid receptors.- TRPV1 and TRPA1 channels and peripheral opioid analgesia.- Role of nanocarriers and tight junction proteins in the delivery of analgesic drugs.- Delineation of central versus peripheral components in the inhibition of clinical pain.

We use histological, biochemical, molecular, electrophysiological and in vivo pain testingmethodologies combined with clinical studies in patients.

Contact:Contact:Contact:Contact:Contact:

Prof. Dr. Christoph SteinKlinik für Anaesthesiologie und operative IntensivmedizinFreie Universität BerlinCharité-Universitätsmedizin BerlinCampus Benjamin FranklinHindenburgdamm 30, D 12200 BerlinTel.: +49 30 8445 2731Fax.: +49 30 8445 4469EMail: christoph.stein@charite.dehttp://anaesthesie.charite.de

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International Graduate PInternational Graduate PInternational Graduate PInternational Graduate PInternational Graduate Program Medical Neurosciencesrogram Medical Neurosciencesrogram Medical Neurosciencesrogram Medical Neurosciencesrogram Medical Neurosciences

The MSc program is divided into 5 modules and a research phase including the Masterthesis. The 1st module is an intensive teaching block covering the neurobiology of thebrain in health and disease from the molecular to the systems level. Module 2 encouragesstudents to develop their individual research focus. In module 3, students are introducedto a number of relevant methods and techniques. A number of complementary skills likestatistical data analysis and communication make up module 4. Students gain their firstpractical lab experience in module 5, the lab rotations. It is in the research phase thatstudents combine the expertise gained in modules 1 to 5 and investigate a set of questionsin great detail, perform experiments, analyze results and write a thesis.

During the 3-year PhD program, students primarily work on their research project in oneof the participating labs. In addition to the lab work, they broaden their neuroscienceexpertise by taking classes and attending colloquia or lecture series. Once a year, PhDstudents organize an international PhD symposium. The PhD degree is awarded based onthree publications or a dissertation.

Speaker: Speaker: Speaker: Speaker: Speaker: Prof. Dr. Ulrich Dirnagl

Contact:Contact:Contact:Contact:Contact:Lutz SteinerKlinik für NeurologieCharité – Universitätsmedizin BerlinSchumannstr. 20/2110117 Berlinwww.medical-neurosciences.de

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Bernstein Center for Computational Neuroscience BerlinBernstein Center for Computational Neuroscience BerlinBernstein Center for Computational Neuroscience BerlinBernstein Center for Computational Neuroscience BerlinBernstein Center for Computational Neuroscience Berlin

The Bernstein Center for Computational Neuroscience Berlin (BCCN Berlin) is acooperation project of Humboldt-Universität zu Berlin, Technische Universität Berlin,Freie Universität Berlin, Charité Universitätsmedizin Berlin, Fraunhofer First, Max-Delbrück-Zentrum and Wissenschaftskolleg zu Berlin. It is funded by the Federal Ministry of Educationand research and part of the National Bernstein Network Computational Neuroscience,Germany.“Precision and Variability” is the research focus of the BCCN Berlin. It addresses to thequestion: “"How is it possible that we can react to sensory stimuli with millisecond precisionif intermediate processing elements – on the level of single synapses, single neurons,small networks and even large neural systems - vary significantly in their response to thesame repeated stimulus?" In particular, the Center studies whether neural variability is aninevitable consequence of the underlying biophysics and thus simply "noise", or whethersuch an interpretation reflects our still limited knowledge about the fundamental principlesof brain-like computation.The Center has established an international Master and PhD Program in ComputationalNeuroscience. The Master Program runs for 2 years and is taught by the faculty of theBCCN Berlin. It is by now in its second year. The PhD Program and the assigned fellowshipsstarted in 2007.

Coordination BCCN Berlin:Coordination BCCN Berlin:Coordination BCCN Berlin:Coordination BCCN Berlin:Coordination BCCN Berlin:Prof. Michael BrechtProf. Laurenz Wiskott

Contact:Contact:Contact:Contact:Contact:Margret FrankeBernstein Center forComputational NeuroscienceHumboldt Universität zu BerlinPhilippstr. 13, Haus 610115 BerlinTel: +49 30 20939110Fax: +49 30 20936771EMail: margret.franke@bccn-berlin.de

Coordination Master & PhD Program:Coordination Master & PhD Program:Coordination Master & PhD Program:Coordination Master & PhD Program:Coordination Master & PhD Program:Prof. Klaus ObermayerProf. Laurenz Wiskott

Contact:Contact:Contact:Contact:Contact:Daniela PelzBernstein Center forComputational NeuroscienceHumboldt Universität zu BerlinPhilippstr. 13, Haus 610115 BerlinTel: +49-30-20936773Fax: +49-30-20936771EMail: graduateprograms@bccn-berlin.de

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Integrated Center for RIntegrated Center for RIntegrated Center for RIntegrated Center for RIntegrated Center for Research and Tesearch and Tesearch and Tesearch and Tesearch and Treatment „reatment „reatment „reatment „reatment „Center forCenter forCenter forCenter forCenter forStroke RStroke RStroke RStroke RStroke Research Berlinesearch Berlinesearch Berlinesearch Berlinesearch Berlin”(CSB),”(CSB),”(CSB),”(CSB),”(CSB),

(BMBF(BMBF(BMBF(BMBF(BMBF-Fördernummer 01 EO 0801)-Fördernummer 01 EO 0801)-Fördernummer 01 EO 0801)-Fördernummer 01 EO 0801)-Fördernummer 01 EO 0801)

The Center for Stroke Research Berlin (CSB) is dedicated to broadening therapy optionsand treading new roads in university medicine with exemplary methods, testing innovativemechanisms on clinically relevant models. In patient care, the CSB will foster anunderstanding of stroke as a chronic disease with heterogeneous causes which can beeffectively met only with an interdisciplinary approach. Conditions for clinical studies atthe CSB, from pre-hospital management to early rehabilitation, have been optimized andclinical research professionalized with young talent being trained specifically as “clinicalscientists”.

CSB research areas:Vascular System: Mechanisms which lead to stroke and thus on the physiology andpathophysiology of the brain's blood supply.Damage and Repair Mechanisms: Mechanisms of tissue damage and cell death, as well asendogenous repair mechanisms. In addition, basic research on mechanisms of regenerationand plasticity are integrated with projects on early and later rehabilitation.Rehabilitation: Rehabilitation and restoration of functional loss.Telemedicine: The use of telemedicine in the acute phase of stroke is going through thetransition from the testing period to routine usage. Telemedicine also opens new vistas inthe areas of the chronic phase and in computer-supported rehabilitation in the patient'sown home.Brain and Immune System: Investigation of the interaction between various body systems.Prototypical examples are the interactions between the brain and the immune system orthe brain and the cardiovascular system.Heart and Brain: Heart disease and stroke share much in common in terms of risk factors,treatment and prognosis.Stroke and Depression: Post-stroke depression is the most common psychiatric complicationafter stroke and could affect up to 50% of patients. The mechanisms have hardly beenresearched.Imaging: Alongside the methods in common use, molecular imaging and non-invasivenear-infrared fluorescence imaging are being explored.

Speaker: Speaker: Speaker: Speaker: Speaker: Prof. Dr. Matthias EndresProf. Dr. Ulrich Dirnagl

Contact:Contact:Contact:Contact:Contact:Dr. Corinna PelzCharité – Universitätsmedizin BerlinCampus Mitte, CC 15, Klinik für NeurologieCharitéplatz 110117 BerlinTel: +49 30 450 560 096Fax: +49 30 450 560 942EMail: corinna.pelz@charite.de

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Competence Network Dementia (CND): Therapy ModuleCompetence Network Dementia (CND): Therapy ModuleCompetence Network Dementia (CND): Therapy ModuleCompetence Network Dementia (CND): Therapy ModuleCompetence Network Dementia (CND): Therapy Module

The Competence Network Dementia (www.kompetenznetz-demenzen.de), founded in2002, is an association of leading german university memory clinics in the field of dementiaresearch.About one million people in Germany are suffering from dementia today. We can expectthat this number increases dramatically within the next decades due to the increasing lifeexpectancy. The CND sets out to improve the medical care of dementia patients byconcentrating research activities and accelerating the transfer of current research findingsinto practical applications. Today, for example the CND has developed and validatednovel biomarkers for Alzheimer dementia in CSF and blood. Most importantly, a centralizedenduring bank of biomaterials (cerebrospinal fluid, serum, DNA etc.), MRT images andclinical data for recruited cases with dementia was established. The combined data- andbiomaterial bank represents one of the worldwide most comprehensive longitudinal followup studies in dementia research.The therapy module of the CND represents a nationwide clinical infrastructure whichcarries out double-blind pharmacological studies in Mild cognitive impairment (MCI) andearly Alzheimers disease (AD).The therapy module of the CND is currently running two clinical trials:1. The AD-Combi study: The primary objective of the AD-Combi trial is to test whether thecombination of Galantamine plus Memantine improves memory/cognitive performanceto a larger extent than Galantamine alone in AD subjects. Co-primary objective is to testwhether the combination is more effective than monotherapy in delaying clinical progressionof dementia. The AD-Combi study was started in 05/2005, recruitment ended in 01/2008. All patients are now in the follow-up observation period. The AD-Combi study willbe completed within the first quarter of 2009.2. The SIMaMCI study: Primary hypothesis of the SIMaMCI trial is to test whetherSimvastatin significantly reduces the conversion rate to Alzheimer’s disease in patientswith MCI as compared to MCI patients receiving placebo. Secondary hypotheses are (1)The benefit from simvastatin treatment is larger in patients with a low level of ß-amyloid /increased level of Tau in CSF as compared to patients above/below the respective cut-offvalues. (2)The benefit from simvastatin treatment is larger in APO-E4 allele carriers thanin other APO-E allele individuals. Recruitment is expected to start in the second half of2008.Both clinical trials are funded by the German Federal Ministry of Education and Research(BMBF).

Speaker:Speaker:Speaker:Speaker:Speaker:Prof. Dr. Isabella Heuser

Contact:Contact:Contact:Contact:Contact:Dr. med. Oliver PetersDepartment of Psychiatry and PsychotherapyCharité – Campus Benjamin FranklinEschenallee 3, 14050 BerlinTel.: +49 30 84458215EMail: oliver.peters@charite.dewww.charite-psychiatry.dewww.kompetenznetz-demenzen.de

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Cortex – Cooperation in RCortex – Cooperation in RCortex – Cooperation in RCortex – Cooperation in RCortex – Cooperation in Research and Tesearch and Tesearch and Tesearch and Tesearch and Training forraining forraining forraining forraining forEuropean Excellence in the NeurosciencesEuropean Excellence in the NeurosciencesEuropean Excellence in the NeurosciencesEuropean Excellence in the NeurosciencesEuropean Excellence in the Neurosciences

Under the acronym of cortex graduate schools in Berlin, Bochum, Helsinki, London, Oslo,Prague, Stockholm, Zurich offer a joint PhD training scheme funded by the EU under theMarie Curie Mobility Action Early Stage Training (EST).Brain cells die following trauma, stroke and in chronic neurodegenerative disease. Themature brain cannot replace lost nerve cells in, and of, itself. An important goal of treatmentand prevention is therefore to minimize nerve cell death. However, recently and quiteunexpectedly, experimental strategies have emerged to foster regeneration in the CNS. Inaddition to understanding the complex mechanisms of brain damage, we must understandhow the nervous system develops and continues to change throughout life. This informationhas profound implications for the treatment of nervous system diseases. Harnessing thecapacity of the nervous system to adapt by reactivating developmental mechanisms allowsfor great hopes in regards to restoring function in the injured or diseased brain. Cortexscientists and students will study the basic mechanisms of damage of common braindisorders as well as the development of the CNS to harness the ability of the CNS to adaptwhen challenged.The cortex neuroscience schools each cover a broad range of neuroscience expertise inthe fields of brain damage, regeneration, and development of the CNS. Bridging from themolecular to the behavioral and clinical level is a common theme of the Cortex partners.However, each cortex member school has one or several unique areas of excellence.Bringing together these complementary fields of excellence within cortex offers youngdoctoral students the entire panoply of neuroscientific possibilities and technologieswhich are available in modern neuroscience, leading to an optimally structured PhD of thehighest quality.The Berlin program has a major focus on translational aspects of neuroscience: ‚bedsideto bench‘, as well as ‚bench to bedside‘. Acute neurodegeneration (stroke),neuroinflammation (MS) and neuroimaging, are key topics on the research agenda.

Contact:Contact:Contact:Contact:Contact:Lutz SteinerKlinik für NeurologieCharité – Universitätsmedizin BerlinSchumannstr. 20/2110117 Berlinwww.cortex-training.net

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Cluster of Excellence “NeuroCure: towards a betterCluster of Excellence “NeuroCure: towards a betterCluster of Excellence “NeuroCure: towards a betterCluster of Excellence “NeuroCure: towards a betterCluster of Excellence “NeuroCure: towards a betteroutcome of neurological disorders.” EXC 257outcome of neurological disorders.” EXC 257outcome of neurological disorders.” EXC 257outcome of neurological disorders.” EXC 257outcome of neurological disorders.” EXC 257

Speaker:Speaker:Speaker:Speaker:Speaker:Prof. Dietmar Schmitz

Contact:Contact:Contact:Contact:Contact:Dr. Tanja RohwederNeuroCure ForschungsmanagementCharité-Universitätsmedizin BerlinCharitéplatz 110117 BerlinTel +49 (0)30 450 539 702Fax +49 (0)30 450 539 970EMail: neurocure@charite.dewww.neurocure.de

Neurological disorders contribute to more than 35% of overall disease burden in Germany,and with an aging society, this number will be increasing further. Therefore, the costs –both for the patients and their loved ones as well as for treatment and long-term healthcare – grow, too. In addition, the current treatments available offer relief at best but nocure. Recently, however, major advances, to which Berlin’s neuroscientists contributedsignifi cantly, have been made in understanding the pathophysiologicial processes underlyingsuch disorders, thereby promising new avenues of intervention that could eventually leadto cure.Responding to such needs, we propose to form NeuroCure, which will serve as aninterdisciplinary consortium and will unite neuroscientists, basic researchers, and cliniciansalike on one campus, independent of their current institutions. NeuroCure will be committedto a strong translational research approach. Due to the wealth of knowledge and acclaimedinternational success of Berlinbased neuroscientists working in the areas of cerebrovasculardiseases, neuroinfl ammation, and disorders of network formation, the initial focus will beon stroke, multiple sclerosis, as well as on focal epilepsies and cns disturbations due tomitochondrial dysfunction. These neurological disorders are known to have overlappingpathophysiological cascades.The ultimate goal of NeuroCure is to bring the benefi ts of our research to society.NeuroCure therefore intends to draw on the combined expertise in clinical trials fromuniversity as well as from non-university institutions and industrial partners to ensure thatour ‘bench-to-bedside’ approach has every chance of success.Building on innovative programs for promoting early-stage scientists (e.g. the GraduateProgram ‘Medical Neurosciences’) and established structures (e.g. theNeurowissenschaftliches Forschungszentrum) as well as core facilities (e.g. the BerlinNeuroImaging Center) for interdisciplinary research, funding of NeuroCure will enableus:* to recruit complementing tenure-track faculty for key research areas* to establish intramural flexible funds to start-up interactive and innovative projectsallocated according to outstanding scientific merit and monitored by peer-review* to set-up an animal research unit for long-term outcome and behavioral analysis * to found the NeuroCure Clinical Research Center (NCRC) inspired by highly successfulcounterparts in the US, and to be the first of its kind in Europe

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Research Unit: Conflicts as Signals in Cognitive SystemsResearch Unit: Conflicts as Signals in Cognitive SystemsResearch Unit: Conflicts as Signals in Cognitive SystemsResearch Unit: Conflicts as Signals in Cognitive SystemsResearch Unit: Conflicts as Signals in Cognitive Systems

The general goal of the research group on "Conflicts as Signals in Cognitive Systems"proceeds from a different assumption, namely that conflicts can be viewed as signals thatare utilized to optimize information processing in the cognitive system.Consequently, our research focuses on increasing our understanding of the interactionbetween conflict signals and subsequent processes of optimization within the system, onunraveling the neuronal implementation of the mechanisms mediating between theregistration of a conflict and subsequent processing modulations, on identifying ontogeneticmodifications of the nature of the interaction between conflicts and processes of optimizationover the life course, and on determining the roles of individual differences and affects inconflict identification and utilization.Conflicts in cognitive systems arise when at least two incompatible behavioral tendenciesor motivations co-exist (Dornette/Pulkowski, 1974).By far most of the existing research on conflicts in cognitive system has been based on theassumption that conflicts reflect incompatible tendencies between inflexible elementaryproperties of the system that were developed in the course of the evolution because ofenvironmental pressures.According to this view, the study of conflicts increases our understanding of the elementaryproperties of cognitive systems. These properties are often assumed to relate to thearchitecture of the system, on the one hand (e.g., limited capacity, simultaneous multi-levelinformation processing), and to processing within the system, on the other hand (e.g.,selection of input information and behavior, differentiation between relevant and non-relevant memory representations).Subprojects:Stephan Brandt (Charité), Herbert Hagendorf (Dept. of Psychology, Humboldt-University):Adaptive Attentional Processing following ConflictPeter Frensch (Dept. of Psychology, Humboldt-University): Conflicts as Triggers forOptimizing StrategiesArthur Jacobs (Dept. of Psychology, Freie Universität): Cognitive-Affective Control inImplicit and Explicit ReproductionUlman Lindenberger und Shu-Chen Li (Max Planck Institute for Live-Span Development):Conflict Monitoring across the Lifespan: Functions and MechanismsWerner Sommer (Dept. of Psychology, Humboldt-University): Emotions in CognitiveConflictsBirgit Stürmer (Dept. of Psychology, Humboldt-University), Stephan Brandt (Charité): Onthe Specificity and Intentionality of Adaptations triggered by ConflictsOliver Wilhelm (Institute for Progress in Education (IQB) Humboldt Universität zu Berlin)Interindividual Differences in overcoming Conflicts in Choice Response Tasks

Speaker:Speaker:Speaker:Speaker:Speaker: Prof. Dr. Werner Sommer; Prof. Dr. Peter Frensch, Dr. Birgit StürmerContact: Contact: Contact: Contact: Contact: Dipl.-Ing. Cornelia ReggentinInstitut für PsychologieHumboldt-Universität zu BerlinRudower Chausee 1812489 BerlinTel. +49 30 2093 4921EMail: cornelia.reggentin@ psychologie.hu-berlin.dehttp://www2.psychologie.hu-berlin.de/konflikte/index.html

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AGING 15, 48ALBUMIN 19, 67, 24ALZHEIMER DISEASE 13, 41ALZHEIMER’S DISEASE 12,15, 16, 23 27, 33, 49, 54AMYLOID 12, 33ANIMAL MODEL 14, 19, 44,67, 69ANXIETY 17, 60APOPTOSIS 15, 24, 51APP 15, 49ASTROCYTE 17, 22, 56, 59ASTROCYTIC ACTIVATION19, 67ATTENTION 16, 18, 56, 61AUDITORY 13, 42AXON 11, 16, 31, 53AXON GUIDANCE 18, 26, 65BASAL GANGLIA 14, 17, 44,57BLOOD FLOW 25BLOOD-BRAIN BARRIER 12,16, 24, 33, 55BRAIN IMAGING 14, 43BRAIN INJURY 13, 26, 38BRAIN SLICE 13, 42CALCIUM 14, 15, 46, 49CALCIUM CHANNEL 11, 29CALCIUM IMAGING 15, 17,18, 50, 62CALCIUM SIGNALLING 22CAM 16, 53CAPILLARIES 13, 38CAR 12, 35CELL CULTURE 17, 59CELL CYCLE 16, 55CELL DEATH 17, 57CELL STRUCTURE 16, 55CEREBELLUM 14, 45CEREBRAL BLOOD FLOW12, 13, 37, 38, 39CEREBRAL BLOOD VESSELS22CEREBRAL CORTEX 18, 65CEREBRAL ISCHEMIA 15, 50CHEMOKINE RECEPTOR14, 43CHLORIDE 11, 31CHOLESTEROL 13, 41CIRCADIAN RHYTHM 16, 56C-MAF 27

CNS 12, 36COGNITION 16, 18, 54, 61,62COLOUR SENSATION 11, 29CONSCIOUSNESS 18, 61CONTROL 13, 41CORTEX 12, 19, 36, 67CULTURE 17, 57CYCLIC GMP 26CYTOKINE 17, 18, 57, 64CYTOSKELETON 15, 47DEGENERATION 27DEMENTIA 16, 54DEMYELINATION 11, 31DENDRITE 11, 12, 13, 32, 35,39DEVELOPMENT 11, 12, 13,15,16, 18, 19, 30, 32, 36, 39, 40,48, 53, 54, 55, 65, 67, 68, 69DOPAMINE 16, 54DORSAL ROOT GANGLION16, 18, 19, 55, 65, 66DRG 11, 26, 29DRINKING 11, 30DYSKINESIA 14, 17, 44, 57ELECTRON MICROSCOPY 24ELECTROPHYSIOLOGY 12,14, 16, 17, 18, 24, 34, 35, 46,55, 58, 61ENDOCYTOSIS 13, 42ENDOTHELIAL 12, 33EPILEPSY 12, 14, 15, 17, 19,25, 27, 37, 46, 50, 58, 67EPILEPTIFORM 19, 68ERP 13, 18, 41, 62EVOKED POTENTIALS 18, 61EXCITABILITY 24EXCITATION 11, 33EXTRACELLULAR 13, 42EXTRACELLULAR MATRIX 12,16, 35, 53FEEDBACK 13, 18, 41, 62FMRI 16, 56FROG SENSITIVE ORGANS11, 33GABA 12, 14, 16, 34, 47, 54GABA RECEPTOR 15, 51GABAERGIC 13, 14, 40, 46GAMMA 14, 15, 43, 51GAP JUNCTION 12, 15, 3, 49

GENE EXPRESSION 13, 40GENE THERAPY 11, 32GENES 23GENETICS 12, 4GFP CHIMERAS 13, 40GLUTAMATE 16, 54GLUTAMATE RECEPTOR 17,56GLYCINE 12, 37GPCR 14, 46GRAY MATTER 12, 34GROWTH FACTOR 24, 26HEARING 14, 43HEAT 16, 52HIPPOCAMPUS 13, 14, 17,19, 39, 44, 58, 68HONEYBEE 13, 18, 38, 65HYPERPOLARIZATION 18, 65HYPOTHERMIA 13, 39HYPOXIA 15, 51IMMUNITY 13, ,18, 25, 38, 62IMMUNOFLUORESCENCE11, 29IMMUNOHISTOCHEMISTRY15, 50IN VITRO 14, 15, 43, 51INFLAMMATION 11, 15, 17,32, 52, 58INHIBITION 12, 37INTERLEUKIN 11, 31INTERNEURON 14, 43ION CHANNEL 13, 15, 18,42, 47, 64ISCHEMIA 12, 37KNOCKOUT MICE 11, 19, 31,66, 68LANGUAGE16, 56LATERAL LINE PATHWAY 19,68LEARNING 13, 16, 18, 19, 38,56, 65, 69LEARNING AND MEMORY12, 13, 36, 39LEARNING AND MEMORY13, 39LOCALIZATION 12, 36MAGNETOENCEPHALOGRAPHY17, 58MECHANORECEPTORS 15,48

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METABOLISM 15, 17, 25, 51,60MICROELECTRODE 16, 53MICROGLIA 11, 12, 13, 17,18, 25, 32, 34, 38, 40, 58, 62MITOCHONDRIA 14, 25, 44,47MOTOR ACTIVITY 17, 58MOTOR CONTROL 17, 57MRI 17, 60MULTIPLE SCLEROSIS 11, 14,18, 19, 31, 43, 62, 67MUSCARINIC 14, 47MUSCLE 12, 17, 33, 60MYELIN 15, 49MYELINATION 27NEURAL STEM CELLS 16, 55NEURITE OUTGROWTH 16,18, 53, 64NEUROBORRELIOSIS 13, 40NEURODEGENERATION 19,25, 67NEUROFILAMENT 12, 35NEUROGENESIS 12, 16, 19,26, 36, 55, 69NEUROIMAGING 16, 54NEUROMUSCULARJUNCTION 16, 53NEURON 13, 15, 19, 25, 40,52, 68NEUROPROTECTION 17, 57NEUROTROPHIN 17, 57NEUROVASCULARCOUPLING 15, 48NK CELLS 14, 43NOCICEPTION 16, 15, 19,48, 52, 66NOISE 14, 43NOREPINEPHRINE 12, 19,36, 68NUMERICALCATEGORIZATION 12, 36OLFACTORY BULB 13, 40OLIGODENDROCYTE 11,15, 31, 49OPTICAL IMAGING 18, 62OPTICAL RECORDING 17,58OSCILLATION 14, 18, 44, 61PAIN 18, 63PARKINSON’S DISEASE 23PATCH CLAMP 15, 50PERICYTES 13, 38PERIPHERIPHAL NERVOUSSYSTEM 27

TRANSPORTER 14, 46TRAUMA 11, 32TRPV1 18, 63TWO PHOTON LASERSCANNING MICROSCOPY22TYROSINE KINASE 16, 52VASCULAR 15, 16, 49, 53VASCULAR 16, 53VIRUS 11, 15, 29, 52VISION 11, 29VOLTAGE CLAMP 11, 18, 30,64XENOPUS LAEVIS 19, 68ZEBRA FINCH 19, 69

PERSONALITY 12, 4PHENOTYPE 17, 60PHOSPHATASE 11, 13, 18, 19,32, 39, 64, 67,PHOSPHOLIPID 18, 63PHOSPHORYLATION 11, 29PLASTICITY 12, 35POTASSIUM 15, 50POTASSIUM CHANNEL 14, 47PRESENILIN 15, 49PROMOTER 13, 40PROTEASE 17, 58PURINERGIC 14, 46PUTAMEN 11, 30RAT 13, 17, 39, 60REINNERVATION 11, 31RETINA 11, 32REWARD 11, 16, 30, 56REWARD 16, 56SENSATION 19, 68SENSITISATION 18, 63SENSORY NEURONS 12, 18,24, 35, 65SEROTONIN 17, 59SIGNAL TRANSDUCTION 11,12, 18, 31, 33, 63, 64SIGNAL TRANSDUCTION 12,33SIGNAL TRANSDUCTION 18,63SIGNAL TRANSDUCTION 18,64SODIUM CHANNEL 11, 30SPINAL CORD INJURY 17, 57SPREADING DEPRESSION12, 15, 16, 37, 49, 53STATUS EPILEPTICUS 19, 66STEM CELL 17, 59STIMULATION 25STROKE 24SYNAPSE 13, 14, 18, 42, 45,63SYNAPTIC PLASTICITY 13, 14,16, 39, 46, 47, 54SYNAPTIC TRANSMISSION14, 17, 19, 45, 47, 56, 66SYNAPTOGENESIS 14, 46TAU 13, 19, 41, 69TAU 19, 69TOLERANCE 11, 32TOXIN 11, 29TRANSFECTION 17, 18, 59,62TRANSGENIC MICE 19, , 66,69

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Author IndexAuthor IndexAuthor IndexAuthor IndexAuthor Index

Adam, Iris 19, 69Ahnert-Hilger, G. 19, 66Aktas, O.2, 19, 67AktasO.16, 55Alam, A. 14, 46Alam, M. 15, 16, 17, 50, 53,58Albus, K. 14, 44Ambrugger, P. 19, 68Andres, C. 11, 29Anirudhan, G. 18, 63Antonio, L.L 17, 58Aoki, J. 14, 46Auer, S. 11, 29Backhaus, W.G.K. 11, 29Basta, D. 2, 13, 14, 43Battefeld, A. 11, 30Bauer, R. 11, 32Bauknecht, C. 14, 43Baumgart, J. 16, 19, 53, 55,66, 67Bechmann, I. 11, 32Beck, A. 11, 16, 30, 56Beck, S. 11, 32Beed, P. 19, 66Behlke, J. 16, 53Behr, J. 13, 39Behrend, O. 11, 19, 33, 68Bendix, I. 11, 16, 31, 55Benedetti, B. 11, 31Berezovska, O. 15, 49Bergthaler, A. 15, 51Bert, B. 17, 60Bertram, L. 10, 23Bharathi, B.S.1, 2, 19, 67Biebermann, H. 19, 68Bierwirth, C. 18, 64Birchmeier, C. 13, 16, 19,27, 40, 52, 66Blankenburg, F. 18, 61Blasig, I.E. 12, 16, 33, 55Boato, F. 11, 31Boese, S. 12, 36Boettcher, C. 11, 13, 32, 40Boettcher, C. 13, 40Bohner, G. 12, 37

Boldakowa, N. 18, 62Bonnas, C. 8, 24Boschmann, M. 17, 60Böttiger, C. 25Brandt, A.U. 18, 62Brandt, C. 11, 32Brandt, N. 11, 13, 32, 39Branoner, F. 11, 19, 33, 68Bräuer, A.U. 12, 14, 18, 19,35, 46, 63, 64, 65, 66, 67Brawanski, A. 26Brück, W. 15, 17, 51, 58Brück, W. 17, 58Brunk, I. 19, 66Brüstle, O. 16, 55Burghoff, M. 15, 17, 48, 58Bushby, K. 12, 33Buttgereit, J. 26Cadavid, D. 13, 40Carl, M. 12, 33Carr, P. 12, 36CastroVillela, V. 12, 33Charbeneau, R. 19, 68Charlet, K. 12, 34Cheung, G. 12, 13, 34, 38Chiang, L.Y. 12, 24, 35Choi, H. B. 22Cholewa, J. 12, 35Coiro, P. 12, 35Craveiro, R.B. 12, 14, 36,45Curio, G. 15, 17, 18, 48,58, 61David, Y.2, 24Deisseroth, K. 7, 21Dembler, T. 16, 54Deng, A. 15, 49Deserno, L.11, 30Diester, I. 12, 36Dietrich, R. 16, 56Dihazi, H. 17, 58Dirnagl, U. 12, 13, 15, 15,37, 38, 39, 51Dorner, A. 16, 53Dörr, J.2, 19, 67Dörr, S.2, 19, 67

Doze, V. 12, 19, 36, 68Dreier, J.P. 12, 15, 16, 30,37, 49, 50, 53,Drenckhahn, C. 12, 37Dugladze, T. 14, 43Dugladze, T. 15, 51Dulinski, M. 16, 53Dvorzhak, A. 14, 46Eichler, S.A. 12, 37Einhäupl, K.M. 12, 37Eisenhardt, D. 13, 18, 38,65Ellinghaus, A. 11, 32Endrass, T. 13, 18, 41, 61,62Engelhardt, B. 10, 21Erdmann, B. 12, 16, 14, 35,52Ernst, A. 13, 14, 42, 43Ertl, M. 26Fabricius, M. 12, 37Färber, K. 12, 13, 18, 34,38, 62Feil, R. 26Felsenberg, J. 13, 38Fernández-Klett, F. 13, 38Fidzinski, P. 13, 14, 17, 39,46, 58Fink, H. 17, 60Flores, L.P.3, 24Frahm, C. 16, 52Frahm, S. 15, 50Franke, K. 13, 39Frenzel, H. 15, 48Freyer, D. 15, 51Friedman, A. 19, 67Friedman, A. 24Frölich, L. 16, 54Füchtemeier, M. 13, 25, 39Gabriel, H.J. 14, 44Gabriel, S. 14, 17, 46, 58Gallinat, J. 12, 16, 34, 56Garratt, A. 13, 16, 27, 40,52Geist, B. 11, 13, 19, 30,40, 66

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Gelderblom, H. 13, 40Gentsch, A. 13, 41Glöckner, F. 13, 41Gloveli, T. 12, 14, 15, 37,43, 51Glumm, R. 16, 55Goetz, J. 19, 69Goldenstein, B. 12, 19,36, 68Goswami, C. 13, 15, 42,47Götze, R. 13, 14, 42, 43Grant G., 22Grantyn, R. 12, 14, 18, 37,46, 47, 63Griffel, C. 16, 52Gröschel, M. 14, 43Grüters-Kieslich, A. 19, 68Gudlowski, Y. 12, 16, 34,43Gurgenidze, S. 14, 43Gutsch, R. 19, 67Haas, B. 11, 31Haggard, P. 7, 21Hamann, I. 14, 43Hamann, M. 14, 44Hanisch, U.K. 17, 58Harms, C. 15, 51Hartings, J.A. 12, 37Haufe, S. 18, 61Hechler, D. 11, 17, 31, 57Hechler, D. 17, 57Heinemann, U. 13, 14, 15,19, 24, 39, 43, 44, 46,47, 51, 58, 67Heinz, A. 11, 12, 16, 30,34, 56Hendrix, S. 11, 17, 31, 57Hentschke, M. 16, 54Heppenstall, P. 14, 16, 27,44, 52Herl, L. 15, 49Hermsdorf, M. 17, 60Herz, J. 18, 62Heuser, I. 16, 17, 54, 59Hofmann, F. 26Homberg, U. 7, 22Horvath, E. 15, 51Hu, J. 8, 12, 16, 19, 24,35, 55, 66

Huang, X. 19, 68Hübner, C.A. 16, 54Hucho, T. 11, 13, 15, 29,42, 47Huchzermeyer, C. 14, 44,47Hyman, B.T. 15, 49Ibanez-Tallon, I. 11, 15, 19,29, 50, 66Infante-Duarte, C. 14, 43Ivens, S. 10, 19, 24, 67Jentsch, T.J. 11, 16, 31, 54Jira, J. 14, 44Jordan, J. 15, 50Jüttner, R. 11, 12, 14, 26,29, 35, 36, 37, 45Kahnt, T. 11, 30Kann, O. 9, 12, 14, 25, 34,44, 47Kathmann, N. 13, 18, 41,61, 62Kaufer, D.3, 24Kaufmann, C. 12, 34Keating, D. 16, 54Kerschensteiner, M. 15, 51Kettenmann, H. 11, 12, 13,15, 17, 18, 31, 34, 38, 49,56, 58, 62Kieselmann, O. 14, 18, 46,63Kim, S. 14, 17, 46, 58Kinne, A. 19, 68Kirischuk, S. 12, 14, 37, 46Kirmse, K. 14, 46, 47Klaft, Z.J. 14, 17, 46, 58Klein, N. 16, 54Klingebiel, R. 14, 43Knudson, C. 12, 36Koch, M. 12, 35Kohl-Bareis, M. 13, 39Kovács, R. 14, 17, 44, 46,47, 58Kreil, A. 14, 44Kröger, S. 16, 53Krueger, C. 25Kubitza, M. 26Kuhn, J. 15, 47Laubisch, D. 25Lauritzen, M. 12, 37Lechner, St.G. 15, 48

Legendre, P. 12, 37Lehmann, T.N. 12, 14, 17,37, 46, 58Lehnardt, S. 8, 25Leistner, S. 15, 17, 48, 58Leite A., L. 14, 46Leithner, C. 13, 25, 39Leuenberger, T. 11, 18, 31,62Lewin, G. 12, 15, 16, 18.19, 24, 35, 48, 50, 52, 55,63, 66Lill, C.M. 15, 49Lindauer, U. 13, 25, 38, 39Londono, D. 13, 40Lorenz, D.16, 54Luebcke, J.17, 56Luger, E.19, 68Macdonald, R. 15, 17, 48,58Macdonald, R.17, 58Mackert, B.M. 15, 17, 48,58Mackert, B.M. 17, 58MacVicar, B. A. 9, 22Maglione, M. 15, 49Mähler, A. 17, 60Maier, H. 16, 54Major, S. 12, 15, 16, 37, 49,53Manning, A.12, 37Markworth, S. 15, 50Maslarova, A. 15, 50Maziashvili, N. 15, 51Megow, D.15, 51Meier, J.C. 12, 37Meier, N. 19, 66Meisel, A. 15, 24, 51Meisel, C. 11, 32Mergenthaler, P.15, 51Merkler, D. 15, 51Meske, V. 13, 41Milenkovic, N. 16, 52Misgeld, T. 9, 15, 23, 51Mitchell, D. 13, 38Möller, H-J.16, 54Möller, T.17, 58Montag, D. 14, 45Moore, S.A. 12, 33Mueller, J. 17, 56

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Müller, E.C. 16, 53Müller, S. 14, 43Müller-Wielsch, K.2, 19, 67Mulligan, S. J. 22Neeb, L. 15, 51Nelson, B. 19, 68Neubig, T. 19, 68Ninnemann, O. 13, 16, 19,40, 55, 66Nitsch, R. 11, 13, 14, 16,17, 18, 19, 25, 30, 31, 32,39, 40, 46, 53, 55, 57, 62,63, 64, 66, 67Nockemann, D. 16, 52Nolte, C. 17, 56Nürnberg, B. 12, 33Offenhauser, N. 10, 13, 25,38, 39Offermanns, S, 18, 63, 64Ohm, T.G. 19, 69Oliveira-Ferreira, A.I. 16,53Otáhal, J. 14, 44Otto, A. 16, 53Otto, W. 16, 53Paesler, D. 14, 17, 46, 58Paterka, M. 14, 16, 43, 53Paul, F.2, 19, 67Pehrs, C. 16, 54Perez, D. 12, 36Peters, O. 16, 17, 54, 59Pfeffer, C. 16, 54Pfueller, C.F. 11, 31Piehl, C. 16, 55Pina, A.L. 10, 26Pinschewer, D. 15, 51Piontek, J. 12, 16, 33, 55Pitarokoili, K. 14, 43Pivneva, T. 17, 56Poole, K. 16, 55Pribula, J. 19, 68Priller, J. 11, 13, 15, 17, 24,32, 38, 40, 51, 59Prinz, M. 17, 58Prozorovski, T. 14, 16, 43,55Pusch, K. 16, 56Radbruch, H. 18, 62Raine, C.S.4, 19, 67Rapp, M.A.16, 56

Rathjen, F.G. 12, 14, 16, 18,26, 35, 36, 45, 53, 65Raue, C. 14, 17, 46, 58Regen, T. 17, 58Renneberg, B. 18, 62Reuter, J.16, 54Reuter, K. 27Rex, A. 17, 60Reyes-Haro, D. 17, 56Richter, A 14, 17, 44, 57Richter, D. 11, 32Rocca, E. 13, 40Rocha, N. 18, 65Röcken, C. 12, 33Ronneberg, T.16, 56Rosenberg, J. 16, 56Rosenberger, K. 11, 17, 31,57Roth, S. 17, 19, 57, 68Royl, G. 13, 25, 39Rückert, C. 12, 33Rudhard, Y. 16, 54Rune, G. 16, 54S Schulz, S. 19, 69Sander, S.E. 17, 57Sander, T.H. 15, 17, 48, 58Sandow, N. 14, 17, 46, 58Schäfermeier, P.K. 12, 37Schäffer, S. 26Schedensack, M. 15, 51Scheffel, J. 17, 58Scheibe, F.17, 59Schipke, C.G. 17, 59Schlagenhauf, F. 16, 56Schlosser, D. 12, 36Schlueter, L. 19, 66Schmidt, H. 8, 9, 16, 18, 26,53, 65Schmidt, N. 17, 60Schmidt, S. 17, 60Schmitz, C.3, 19, 67Schmitz, D. 19, 66Schott, E. 25Schreiber, M. 18, 61Schröter, F. 16, 55Schubert, F. 12, 34Schubert, R. 18, 61Schuchmann, S. 19, 66Schuelke, M. 19, 66Schuermann, B. 18, 62

Schuldt, C. 11, 19, 33, 68Schulte, S.16, 56Schulze-Topphoff, U. 11, 16,18, 31, 55, 62Schumacher, S. 11, 13, 16,32, 39, 53Schweizer, U. 17, 57Schweizer, U. 8, 19, 27, 68Seeliger, M.W. 11, 32Seifert, S. 18, 62Sendtner, M. 19, 66Siegert, E. 16, 55Siffrin, V. 11, 18, 31, 62SingBal, M. 12, 33Singh, B. 14, 18, 46, 63Skreka, K.17, 57Smith, E.St.J. 18, 63Sommer, W.16, 56Soriguera, A. 18, 63, 64Spahn, V. 18, 64Spuler, S. 12, 17, 3360Stadler, K. 18, 64Stein, C. 16, 52Stein, V. 16, 54Steinbrink, J. 12, 13, 37, 39Stollhoff, N. 18, 65Stonkute, A. 18, 16, 65Stradomska, A.M. 14, 45Strauss, U. 11, 18, 30, 64,65Streu, N. 19, 66Strong, 12, 37Stürzebecher, A. 19, 66Swiercz, J. 18, 63Swiercz, J.M. 18, 64Taubenberger, N. 14, 44, 47Thomas, A.V. 15, 49Tolias, C. 12, 37Trahms, L. 15, 17, 48, 58Tress, O. 15, 49Trimbuch, T. 13, 19, 25, 49,66Tsokos, M.5, 19, 67Uckert, W. 18, 62Ullsperger, M. 13, 41Ullsperger, P. 13, 41Unsoeld, T.14, 45Vajkoczy, P. 7, 12, 37vanRossum, D. 17, 58VanWagenen, S. 26

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Velmans, T. 12, 35Velmans, T. 19, 67Villringer, A. 18, 61Vogt, J. 17, 19, 60, 66, 67Voitcu, R.N. 19, 24, 67Voss, M. 16, 54Wabnitz, H. 15, 17, 48, 58Wabnitz, H. 17, 58Waiczies, S. 11, 31Wald, J.19, 68Wallis, R. 13, 38Wang, R. 14, 15, 45,48Wasner, U. 11, 30Weber, J. 25Weber, M.A. 17, 60Weinshenker, D. 19, 68Weinstein, J.R. 17, 58Wende, H. 10, 27Werr, J. 18, 62Wichmann, F. A. 7, 23Willecke, K. 15, 49Winkler, L.16, 55Wirth, E.K. 17, 19, 57, 68Woitzik, J. 12, 37Wrase, J. 11, 30Wrase, J. 16, 56Wulczyn, F.G. 16, 25, 53Xu, K. 19, 68Zabojszcza, J. 12, 33Zhivkov, Z. 11, 19, 33, 68Ziehm, U. 11, 33Zipp, F. 11, 14, 16, 18, 19,31, 43, 55, 62, 67Zöllner, C.18, 64Zonnur, S. 19, 69Zurborg, S. 27

Author IndexAuthor IndexAuthor IndexAuthor IndexAuthor Index

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Address ListAddress ListAddress ListAddress ListAddress List

Andres, Christ ineAndres, Christ ineAndres, Christ ineAndres, Christ ineAndres, Christ ineDepartment RopersMax Planck Institute for Molecular GeneticsIhnestr. 63-7314195 BerlinE Mail: andres@molgen.mpg.de

AuerAuerAuerAuerAuer, Sebastian, Sebastian, Sebastian, Sebastian, SebastianDepartment of NeurobiologyMax-Delbrück Center for Molecular MedicineRobert-Rössle-Str. 1013125 BerlinE Mail: auer.sebastian@mdc-berlin.de

Backhaus, DrBackhaus, DrBackhaus, DrBackhaus, DrBackhaus, Dr. W. W. W. W. Werner Gerner Gerner Gerner Gerner G. K. K. K. K. K.....Theoretische und Experimentelle Biologie,Neurowissenschaften, FR 2-1 R 2073Technische Universität BerlinFranklinstr. 28 - 2910587 BerlinTel.: +49 30 314 73614E Mail: backhaus@zedat.fu-berlin.de

Bastos Craveiro, RogérioBastos Craveiro, RogérioBastos Craveiro, RogérioBastos Craveiro, RogérioBastos Craveiro, RogérioNeurobiologyMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössler-Strasse 1013092 BerlinE Mail: craveiro@mdc-berlin.de

Battefeld, ArneBattefeld, ArneBattefeld, ArneBattefeld, ArneBattefeld, ArneCentre for Anatomy, Institute for Cell and NeurobiologyCharité Universitätsmedizin BerlinCharitéplatz 110117 BerlinTel.: +49 30 450 528027E Mail: arne.battefeld@charite.de

Bendix, IvoBendix, IvoBendix, IvoBendix, IvoBendix, IvoCecile Vogt Clinic for Neurology at the HKBBCharite University Medicine BerlinCharitéplatz 0110117 BerlinTel.: +49 30 539051E Mail: ivo.bendix@charite.de

Benedetti, BrunoBenedetti, BrunoBenedetti, BrunoBenedetti, BrunoBenedetti, BrunoCellular NeuroscienceMax-Delbrück-Centrum für Molekulare MedizinRobert Rössle Str. 1013092 BerlinTel.: +49 30 9406 3503E Mail: Bruno.Benedetti@mdc-berlin.de

Bengtsson, DrBengtsson, DrBengtsson, DrBengtsson, DrBengtsson, Dr. L. L. L. L. LuizauizauizauizauizaAG JentschMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössle Str 1013125 BerlinE Mail: luiza.bengtsson@mdc-berlin.de

Bertram, DrBertram, DrBertram, DrBertram, DrBertram, Dr. L. L. L. L. LarsarsarsarsarsGenetics and Aging Research UnitMassachussetts General Institute forNeurodegenerative Disease (MIND)114, 16th Street, Rm. 3800MA 02129 Charlestown (USA)Tel.: +1 617 724 5567E Mail: bertram@helix.mgh.harvard.edu

Bill ig, GwendolynBil l ig, GwendolynBil l ig, GwendolynBil l ig, GwendolynBil l ig, GwendolynPhysiology and Pathology of Ion TransportFMP/ Max-Delbrück-Centrum für MolekulareMedizinRobert-Rössle-Str. 1013125 BerlinTel.: +49 30 9406 3019E Mail: gbillig@fmp-berlin.de

Blazej, KatjaBlazej, KatjaBlazej, KatjaBlazej, KatjaBlazej, KatjaMolekulare PsychiatrieCharite Campus MitteCharitéplatz 110117 BerlinTel.: +49 30 450 560184E Mail: katja.blazej@charite.de

Boato, FrancescoBoato, FrancescoBoato, FrancescoBoato, FrancescoBoato, FrancescoInstitute for Cell Biology and Neurobiology,Center for AnatomyCharité – UniversitätsmedizinPhilippstrasse10115 BerlinTel.: +49 17625693531E Mail: fraboato@hotmail.com

BoettcherBoettcherBoettcherBoettcherBoettcher, Dr, Dr, Dr, Dr, Dr. Chotima. Chotima. Chotima. Chotima. ChotimaLaboratory of Molecular PsychiatryCharité Campus MitteSchumannstr. 20/2110117 BerlinTel.: +49 30 450 560184E Mail: chotima.boettcher@charite.de

Bött igerBött igerBött igerBött igerBött iger, Caroline, Caroline, Caroline, Caroline, CarolineChariteExperimental NeurologyChariteplatz 110098 BerlinE Mail: caroline.boettiger@charite.de

Bonnas, ChristelBonnas, ChristelBonnas, ChristelBonnas, ChristelBonnas, ChristelExperimentelle NeurologieMolekulare PsychiatrieCharité (CCM)Charitéplatz 110117 BerlinTel.: +49 30 450 560184E Mail: christel.bonnas@charite.de

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BräuerBräuerBräuerBräuerBräuer, P, P, P, P, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. Anja U. Anja U. Anja U. Anja U. Anja U.....Centrum for AnatomyCharité, Institute for Cell Biology and NeurobiologyPhillipstr 1210115 BerlinTel.: +49 30 450 528405E Mail: anja.braeuer@charite.de

Brandt, NicolaBrandt, NicolaBrandt, NicolaBrandt, NicolaBrandt, NicolaCharité-Universitätsmedizin Berlin, Center for AnatomyInstitute of Cell Biology and NeurobiologyPhilippstr. 1210115 BerlinTel.: +49 30 4505 28124E Mail: nicola.brandt@charite.de

Brandt, DrBrandt, DrBrandt, DrBrandt, DrBrandt, Dr. Christ ine. Christ ine. Christ ine. Christ ine. Christ ineCenter for AnatomyInstitute of Cellbiology and NeurobiologyChariteplatz 110117 BerlinTel.: +49 30 450 528090E Mail: christine.brandt@charite.de

BranonerBranonerBranonerBranonerBranoner, F, F, F, F, FranciscoranciscoranciscoranciscoranciscoInstitute of Biology, Aquatic Bioacoustics LaboratoryHumboldt Universität BerlinInvalidenstr. 4310115 BerlinTel.: +49 30 2093 8861E Mail: mail@francisco-branoner.de

Broich, MarkusBroich, MarkusBroich, MarkusBroich, MarkusBroich, MarkusPAA Laboratories GmbHUnterm Bornrain 235091 CölbeTel.: +49 30 4606 5273E Mail: m.broich@paa.com

Bulavina, LarisaBulavina, LarisaBulavina, LarisaBulavina, LarisaBulavina, LarisaMax-Delbrück-CentrumRobert-Roessle-Str.1013125 BerlinE Mail: larisa.bulavina@mdc-berlin.de

Carl, MiriamCarl, MiriamCarl, MiriamCarl, MiriamCarl, MiriamMuscle Research UnitExperimental and Clinical Research Center (ECRC),Charité Universitary Medical SLindenberger Weg 8013125 BerlinTel.: +49 30 9417 15E Mail: miriam.carl@charite.de

Castro Vil lela, Victor M.Castro Vil lela, Victor M.Castro Vil lela, Victor M.Castro Vil lela, Victor M.Castro Vil lela, Victor M.Molecular Cell PhysiologyLeibniz-Institut für Molekulare PharmakologieRobert-Rössle Str.13127 BerlinE Mail: castro@fmp-berlin.de

Charlet, KarinCharlet, KarinCharlet, KarinCharlet, KarinCharlet, KarinDepartment of Psychiatry and Psychotherapy CampusMitteCharité - University Medicine BerlinTelramundweg 1412167 BerlinTel.: +49 1638679454E Mail: mailfreeze@gmail.com

Cheung, GiselleCheung, GiselleCheung, GiselleCheung, GiselleCheung, GiselleCellular NeuroscienceMax-Delbrück-Centrum für Molekulare MedizinRobert-Roessle-Str. 1013125 BerlinTel.: +49 30 9406 3503E Mail: gcheung@mdc-berlin.de

ChiangChiangChiangChiangChiang, Li-, Li-, Li-, Li-, Li-YYYYYangangangangangNeuroscienceMax-Delbrück CentrumRobert-Rössle-Str.1013125 BerlinTel.: +49 30 9406 3783E Mail: li-yang.chiang@mdc-berlin.de

Chiu, JazminChiu, JazminChiu, JazminChiu, JazminChiu, JazminInstitute for Experimental Endocrinology andNeuroscience Research CenterCharitéChariteplatz 110117 BerlinE Mail: jazmin.chiu@charite.de

Cholewa, JadwigaCholewa, JadwigaCholewa, JadwigaCholewa, JadwigaCholewa, JadwigaDevelopmental NeurobiologyMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössle-Str. 1013125 BerlinE Mail: jadwiga.cholewa@mdc-berlin.de

Coiro, PierlucaCoiro, PierlucaCoiro, PierlucaCoiro, PierlucaCoiro, PierlucaInstitut für Zell- und NeurobiologieCharitePhilippstraße 1210115 BerlinTel.: +49 30 450 528343E Mail: luca_coiro@yahoo.it

Colla, DrColla, DrColla, DrColla, DrColla, Dr. Michael. Michael. Michael. Michael. MichaelDepartment of PsychiatryCharite Campus Benjamin FranklinEschenallee 314050 BerlinTel.: +49 30 8445 8407E Mail: michael.colla@charite.de

Curio, PCurio, PCurio, PCurio, PCurio, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. Gabriel. Gabriel. Gabriel. Gabriel. GabrielAG Neurophysik, Klinik für NeurologieCharité - Campus Benjamin FranklinHindenburgdamm 3012200 BerlinTel.: +49 30 8445 4706E Mail: gabriel.curio@charite.de

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Deisseroth, PDeisseroth, PDeisseroth, PDeisseroth, PDeisseroth, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. K. K. K. K. KarlarlarlarlarlBioengineering, Dept. of PsychiatryStanford University, Clark Center WO83318 Campus Drive WestCA 94305 Stanford (USA)E Mail: deissero@gmail.com

Deserno, LorenzDeserno, LorenzDeserno, LorenzDeserno, LorenzDeserno, LorenzDepartment of Psychiatry and PsychotherapyCharité - Universitätsmedizin Berlin, CCMPaul-Robeson-Str. 3410439 BerlinTel.: +49 30 405 28930E Mail: lorenzdeserno@web.de

DiesterDiesterDiesterDiesterDiester, I lka, I lka, I lka, I lka, I lkaCognitive NeurologyHertie Institute for Clinical Brain ResearchOtfried-Müller-Str. 2772074 TübingenTel.: +49 7071 29 81935E Mail: ilka.diester@uni-tuebingen.de

Dirnagl, PDirnagl, PDirnagl, PDirnagl, PDirnagl, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. Ulrich. Ulrich. Ulrich. Ulrich. UlrichExp. NeurologyChariteCharitepl.110098 BerlinE Mail: ulrich.dirnagl@charite.de

Doze, DrDoze, DrDoze, DrDoze, DrDoze, Dr. V. V. V. V. VanananananPharmacology, Physiology TherapeuticsUniv. of North Dakota School of Medicine HealthSciences501 N Columbia Rd58203 Grand Forks, North Dakota (USA)Tel.: +1 701 777 6222E Mail: vdoze@medicine.nodak.edu

DreierDreierDreierDreierDreier, PD Dr, PD Dr, PD Dr, PD Dr, PD Dr. Jens P. Jens P. Jens P. Jens P. Jens P.....NeurologyCharité University Medicine BerlinCharitépl. 110117 BerlinTel.: +49 30 4506 60024E Mail: jens.dreier@charite.de

EichlerEichlerEichlerEichlerEichler, Sabrina, Sabrina, Sabrina, Sabrina, SabrinaNeuroscienceMax-Delbrück-Centrum für Molekulare MedizinRobert-Roessle-Str. 1013092 BerlinE Mail: sabrina.eichler@mdc-berlin.de

Eisenhardt, DrEisenhardt, DrEisenhardt, DrEisenhardt, DrEisenhardt, Dr. Dorothea. Dorothea. Dorothea. Dorothea. DorotheaNeurobiologieFreie Universität BerlinKönigin-Luise-Str. 28/3014195 BerlinTel.: +49 30 838 56781E Mail: theodora@neurobiologie.fu-berlin.de

Endres, PEndres, PEndres, PEndres, PEndres, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. med Matthias. med Matthias. med Matthias. med Matthias. med MatthiasNeurology UKBFCharitéHindenburgdamm 3012200 BerlinTel.: +49 30 8445 2277E Mail: matthias.endres@charite.de

Engelhardt, PEngelhardt, PEngelhardt, PEngelhardt, PEngelhardt, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. Brit ta. Brit ta. Brit ta. Brit ta. Brit taTheodor Kocher InstititeUniversity of BernFreiestraße 13012 Bern (Switzerland)Tel.: +41 31 631 4143E Mail: bengel@tki.unibe.ch

FärberFärberFärberFärberFärber, Dr, Dr, Dr, Dr, Dr. K. K. K. K. KatrinatrinatrinatrinatrinCellular NeuroscienceMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössle-Str. 1013125 BerlinTel.: +49 30 9406 3260E Mail: kfaerber@mdc-berlin.de

FFFFFelsenbergelsenbergelsenbergelsenbergelsenberg, Dr, Dr, Dr, Dr, Dr. Johannes. Johannes. Johannes. Johannes. JohannesNeurobiologieFreie Universität BerlinKönigin-Luise-Str. 28/3014195 BerlinTel.: +49 30 838 56781E Mail: johannesfelsenberg@mgx.de

Fernandez Klett, FranciscoFernandez Klett, FranciscoFernandez Klett, FranciscoFernandez Klett, FranciscoFernandez Klett, FranciscoDepartment of Experimental NeurologyCharité - Universitätsmedizin BerlinCharitéplatz 110117 BerlinTel.: +49 30 450 517 17E Mail: francisco.fernandez@charite.de

FFFFFidzinski, Dridzinski, Dridzinski, Dridzinski, Dridzinski, Dr. P. P. P. P. PawelawelawelawelawelInstitute for NeurophysiologyCharité UniversitaetsmedizinTucholskystr. 210117 BerlinTel.: +49 30 450 528209E Mail: pawel.fidzinski@charite.de

FFFFFrahm, Drrahm, Drrahm, Drrahm, Drrahm, Dr. Silke. Silke. Silke. Silke. Silkemolecular neurobiologyMax-Delbrueck-CentrumRobert-Roessle_Str. 1013125 BerlinE Mail: sfrahm@mdc-berlin.de

Franke, Krist inFranke, Krist inFranke, Krist inFranke, Krist inFranke, Krist inCharité-Universitätsmedizin Berlin; Centre for AnatomyInstitute of Cell Biology and NeurobiologyPhilippstrasse 1210115 BerlinTel.: +49 30 4505 2812E Mail: kristin.franke@charite.de

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FüchtemeierFüchtemeierFüchtemeierFüchtemeierFüchtemeier, Martina, Martina, Martina, Martina, MartinaDepartment of Experimental NeurologyCharite Universitätsmedizin BerlinChariteplatz 110098 BerlinE Mail: martina.fuechtemeier@charite.de

Garratt, DrGarratt, DrGarratt, DrGarratt, DrGarratt, Dr. Alistair. Alistair. Alistair. Alistair. AlistairDepartment of NeurosciencesMax-Delbrueck-Center for Molecular MedicineRobert-Roessle-Strasse 1013125 BerlinTel.: +49 30 9406 3785E Mail: agarratt@mdc-berlin.de

Geist, BeateGeist, BeateGeist, BeateGeist, BeateGeist, BeateInstitut für Zell- und NeurobiologieCharité-Universitätsmedizin Berlin, Center für AnatomieChariteplatz 110117 BerlinTel.: +49 30 450528 008E Mail: beate.geist@charite.de

Gelderblom, DrGelderblom, DrGelderblom, DrGelderblom, DrGelderblom, Dr. Harald. Harald. Harald. Harald. HaraldMolekulare PsychiatrieCharite-Klinik f. Psychiatrie u. Psychotherapie, ChariteCampus MitteCharitéplatz 110117 BerlinTel.: +49 30 4505 17239E Mail: harald.gelderblom@charité.de

Gentsch, AntjeGentsch, AntjeGentsch, AntjeGentsch, AntjeGentsch, AntjeWolliner Str. 16A10435 BerlinE Mail: antjegentsch@googlemail.com

GlöcknerGlöcknerGlöcknerGlöcknerGlöckner, F, F, F, F, FraukeraukeraukeraukeraukeZentrum für AnatomieCharité-Universitätsmedizin BerlinPhilippstr.10117 BerlinE Mail: frauke.gloeckner@charite.de

Götze, RomyGötze, RomyGötze, RomyGötze, RomyGötze, RomyDepartment of Biology, Neurootological TeamHumboldt-University BerlinPhilippstraße 13, Haus 210115 BerlinE Mail: romy.goetze@biologie.hu-berlin.de

Goswami, DrGoswami, DrGoswami, DrGoswami, DrGoswami, Dr. Chandan. Chandan. Chandan. Chandan. ChandanSignal Transduction in Pain and Mental RetardationMax Planck Institute for Molecular GeneticsIhnestrasse 7314195 BerlinE Mail: goswami@molgen.mpg.de

Grantyn, PGrantyn, PGrantyn, PGrantyn, PGrantyn, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. R. R. R. R. RosemarieosemarieosemarieosemarieosemarieDevelopmental PhysiologyInst. for Neurophysiology - CharitéTucholskystr. 210117 BerlinE Mail: rosemarie.grantyn@gmx.de

Gröschel, MoritzGröschel, MoritzGröschel, MoritzGröschel, MoritzGröschel, MoritzInstitute of BiologyHumboldt-University of BerlinPhilippstr. 13, Haus 210115 BerlinE Mail: moritz.groeschel@biologie.hu-berlin.de

Gurgenidze, ShalvaGurgenidze, ShalvaGurgenidze, ShalvaGurgenidze, ShalvaGurgenidze, ShalvaCharite Universitätsmedizin BerlinInstitute for NeurophysiologyTucholskystr. 210117 BerlinTel.: +49 30 450 528376E Mail: schakoscha@yahoo.de

Haggard, PHaggard, PHaggard, PHaggard, PHaggard, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. P. P. P. P. PatrickatrickatrickatrickatrickInstitute of Cognitive NeuroscienceUniversity College London17 Queen SquareWC1N 3AR London (UK)Tel.: +44 207 679 1153E Mail: p.haggard@ucl.ac.uk

Hamann, DrHamann, DrHamann, DrHamann, DrHamann, Dr. Melanie. Melanie. Melanie. Melanie. MelanieFreie Universität Berlin, Dept. of Veterinary MedicineInstitute of Pharmacology and ToxicologyKoserstraße 2014195 BerlinTel.: +49 30 838 53513E Mail: Hamann.Melanie@vetmed.fu-berlin.de

Hamann, IsabellHamann, IsabellHamann, IsabellHamann, IsabellHamann, IsabellCecilie Vogt Clinic of NeurologyCharité - University Medicine BerlinCharitéplatz 110117 BerlinTel.: +49 30 450 539051E Mail: isabell.hamann@charite.de

Hanisch, PHanisch, PHanisch, PHanisch, PHanisch, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. Uwe. Uwe. Uwe. Uwe. Uwe-K-K-K-K-KarstenarstenarstenarstenarstenInstitute of NeuropathologyUniversity of GöttingenRobert-Koch-Straße 4037075 GöttingenTel.: +49 551 396 520E Mail: ukhanisch@med.uni-goetingen.de

Heidenreich, MatthiasHeidenreich, MatthiasHeidenreich, MatthiasHeidenreich, MatthiasHeidenreich, MatthiasPhysiology and Pathology of Ion TransportMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössle-Strasse 1013125 BerlinE Mail: matthias.heidenreich@mdc-berlin.de

Heinemann, PHeinemann, PHeinemann, PHeinemann, PHeinemann, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. Uwe. Uwe. Uwe. Uwe. UweNeurophysiologyCharité Universitaetsmedizin BerlinTucholskystr. 210117 BerlinTel.: +49 30 450 528091E Mail: uwe.heinemann@charite.de

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Hendrix, PD DrHendrix, PD DrHendrix, PD DrHendrix, PD DrHendrix, PD Dr. Sven. Sven. Sven. Sven. SvenInstitute for Cell Biology and NeurobiologyCenter for Anatomy, Charité - Universitätsmedizin BerlinCharitepl. 110117 BerlinTel.: +49 30 450 528 40E Mail: sven.hendrix@charite.de

Herz, JosephineHerz, JosephineHerz, JosephineHerz, JosephineHerz, JosephineCecilie Vogt Clinic for Neurology at the HELIOS ClinicBerlin-Buch, Scientific DCharité - Universitätsmedizin Berlin, Max DelbrückCenter for Molecular MedicineCharitéplatz 110117 BerlinTel.: +49 30 450 539057E Mail: josephine.herz@charite.de

Heydt, MiriamHeydt, MiriamHeydt, MiriamHeydt, MiriamHeydt, MiriamCharitéMedizinische ImmunologieMonbijou Straße 2a10117 BerlinTel.: +49 30 450524195E Mail: miriamheydt@hotmail.com

Hoang, Ha ThiHoang, Ha ThiHoang, Ha ThiHoang, Ha ThiHoang, Ha ThiCharité - Int. Graduate Program MedicalNeuroscienceSwinemuender Str. 1110435 BerlinE Mail: hoang.hathi@gmail.com

HombergHombergHombergHombergHomberg, P, P, P, P, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. Uwe. Uwe. Uwe. Uwe. UweFachbereich Biologie, TierphysiologieUniversität MarburgKarl von Frisch Str. 835032 MarburgTel.: +49 6421 2823402E Mail: homberg@staff.uni-marburg.de

Hu, DrHu, DrHu, DrHu, DrHu, Dr. Jing. Jing. Jing. Jing. JingNeuroscienceMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössle-Str.1013125 BerlinTel.: +49 30 9406 3783E Mail: jinghu@mdc-berlin.de

Hucho, DrHucho, DrHucho, DrHucho, DrHucho, Dr. T. T. T. T. TimimimimimMax Planck Institute for Molecular GeneticsIhnestrasse 7314195 BerlinTel.: +49 30 8413 1243E Mail: hucho@molgen.mpg.de

HuchzermeyerHuchzermeyerHuchzermeyerHuchzermeyerHuchzermeyer, Christ ine, Christ ine, Christ ine, Christ ine, Christ ineCharité, Institut für NeurophysiologieTucholskystraße 210117 BerlinE Mail: christine.huchzermeyer@charite.de

InfanteInfanteInfanteInfanteInfante -Duarte, Dr-Duarte, Dr-Duarte, Dr-Duarte, Dr-Duarte, Dr. Carmen. Carmen. Carmen. Carmen. CarmenCecilie-Vogt-Klinik für NeurologieCharite - Universitätsmedizin BerlinCharitéplatz 110117 BerlinTel.: +49 30 450 539055E Mail: carmen.infante@charite.de

Ivens, SebastianIvens, SebastianIvens, SebastianIvens, SebastianIvens, SebastianInstitut für NeurophysiologieCharité Unverisitätsmedizin BerlinTucholskystraße 210117 BerlinTel.: +49 30 450 528383E Mail: sivens@gmail.com

Jabs, SabrinaJabs, SabrinaJabs, SabrinaJabs, SabrinaJabs, SabrinaPhysiology and Pathology of Ion TransportFMP/ Max-Delbrück-Centrum für Molekulare MedizinRobert-Rössle-Str.1013125 BerlinTel.: +49 30 9406 3021E Mail: sabrina.jabs@mdc-berlin.de

Jira, JuliaJira, JuliaJira, JuliaJira, JuliaJira, JuliaKlinik fuer AnaesthesiologieCharité CBFHindenburgdamm 3012200 BerlinTel.: +49 30 844 52131E Mail: julia.jira@charite.de

JüttnerJüttnerJüttnerJüttnerJüttner, Dr, Dr, Dr, Dr, Dr. R. R. R. R. ReneeneeneeneeneMax-Delbrück-Centrum für Molekulare MedizinDevelopmental NeurobiologyRobert-Rössle Str. 1013092 BerlinTel.: +49 30 9406 2772E Mail: r.juettner@mdc-berlin.de

KKKKKann, Drann, Drann, Drann, Drann, Dr. Oliver. Oliver. Oliver. Oliver. OliverNeurophysiologyCharité-Universitätsmedizin BerlinTucholskystrasse 210117 BerlinTel.: +49 30 450 528357E Mail: oliver.kann@charite.de

KKKKKettenmann, Pettenmann, Pettenmann, Pettenmann, Pettenmann, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. Helmut. Helmut. Helmut. Helmut. HelmutZelluläre NeurowissenschaftenMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössle-Str. 1013125 BerlinTel.: +49 30 9406 3325E Mail: jarchow@mdc-berlin.de

Kieselmann, OlgaKieselmann, OlgaKieselmann, OlgaKieselmann, OlgaKieselmann, OlgaCell- and NeurobiologyCharité, Centrum for AnatomyCharitéplatz 110117 BerlinTel.: +49 30 4505 28043E Mail: olga.kieselmann@charite.de

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Kim, SimonKim, SimonKim, SimonKim, SimonKim, SimonCharité, Institut für NeurophysiologieTucholskystr. 210117 BerlinE Mail: simon.kim@charite.de

Kirischuk, DrKirischuk, DrKirischuk, DrKirischuk, DrKirischuk, Dr. Sergei. Sergei. Sergei. Sergei. SergeiDevelopmental PhysiologyInstitut für Neurophysiolgie, Charité-Universität-MedizinBerlinTucholskystr. 210117 BerlinTel.: +49 30 450 528102E Mail: sergei.kirischuk@charite.de

Kloetzel, PKloetzel, PKloetzel, PKloetzel, PKloetzel, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. P. P. P. P. PeteretereteretereterInstitute of BiochemistryCharité Berlin CCMMonbijoustr. 210117 BerlinTel.: +49 30 4505 28071E Mail: p-m.kloetzel@charite.de

KKKKKovacs, Drovacs, Drovacs, Drovacs, Drovacs, Dr. Richard. Richard. Richard. Richard. RichardInst. for NeurophysiologyCharite-Universitaetsmedizin, BerlinTucholskystr. 210117 BerlinTel.: +49 30 450 528357E Mail: richard.kovacs@charite.de

Kuhn, JuliaKuhn, JuliaKuhn, JuliaKuhn, JuliaKuhn, JuliaMPI for Molecular GeneticsIhnestr. 63-7314195 BerlinE Mail: kuhn@molgen.mpg.de

Laqua, MartinLaqua, MartinLaqua, MartinLaqua, MartinLaqua, MartinMolecular NeurobiologyMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössle-Str. 1013092 BerlinE Mail: laqua@mdc-berlin.de

LLLLLechnerechnerechnerechnerechner, Dr, Dr, Dr, Dr, Dr. Stefan. Stefan. Stefan. Stefan. StefanNeurowisssenschaftenMax Delbrück Centrum für Molekulare MedizinRobert Rössle Str. 1013125 BerlinTel.: +49 30 9406 2853E Mail: sg.lechner@mdc-berlin.de

LLLLLehnardt, Drehnardt, Drehnardt, Drehnardt, Drehnardt, Dr. Seija. Seija. Seija. Seija. SeijaCecilie-Vogt-Klinik für Neurologie im HKBBCharité-UniversitätsmedizinCharitéplatz 110117 BerlinTel.: +49 30 450 528090E Mail: seija.lehnardt@charite.de

Leisle, Li l iaLeisle, Li l iaLeisle, Li l iaLeisle, Li l iaLeisle, Li l iaAG JentschMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössle-Str. 1013125 BerlinE Mail: lleisle@fmp-berlin.de

LLLLLeistnereistnereistnereistnereistner, Dr, Dr, Dr, Dr, Dr. Stefanie. Stefanie. Stefanie. Stefanie. StefanieDepartment of NeurologyCharité, Campus Benjamin FranklinHindenburgdamm 3012200 BerlinTel.: +49 30 17356153E Mail: stefanie.leistner@charite.de

LLLLLeuenbergereuenbergereuenbergereuenbergereuenberger, T, T, T, T, TinainainainainaCecilie Vogt Clinic for Neurology in the HKBBCharite-University Medicine BerlinChariteplatz 110117 BerlinTel.: +49 30 450 539051E Mail: tina.leuenberger@charite.de

LLLLLewin, Pewin, Pewin, Pewin, Pewin, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. Gary. Gary. Gary. Gary. GaryNeurosciencesMax Delbrück Center for Molecular MedicineRobert-Rössle-Str. 1013125 BerlinTel.: +49 30 9406 2430E Mail: glewin@mdc-berlin.de

Lil l, Christ inaLil l, Christ inaLil l, Christ inaLil l, Christ inaLil l, Christ inaNeurologyCecilie Vogt Clinic for Neurology, Charité BerlinChariteplatz 110117 BerlinE Mail: christina.lill@charite.de

MacVicarMacVicarMacVicarMacVicarMacVicar, P, P, P, P, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. Brian A.. Brian A.. Brian A.. Brian A.. Brian A.Department of Psychiatry, Brain Research CenterUBC Hospital, Loerner Pavillon2211 Wesbrook MallV6T 2B5 Vancouver, BC (Canada)Tel.: +1 604 822 7797E Mail: bmacvica@interchange.ubc.ca

Maglione, MartaMaglione, MartaMaglione, MartaMaglione, MartaMaglione, MartaCellular NeuroscienceMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössle-Str 1013125 BerlinTel.: +49 30 9406 3503E Mail: m.maglione@mdc-berlin.de

MajorMajorMajorMajorMajor, Sebastian, Sebastian, Sebastian, Sebastian, SebastianExperimental NeurologyCharité -Universitätsmedizin BerlinCharitéplatz 110117 BerlinTel.: +49 30 450 560 00E Mail: sebastian.major@charite.de

Margulies, DanielMargulies, DanielMargulies, DanielMargulies, DanielMargulies, DanielBerlin School of Mind and BrainHumboldt UniversityNaunynstrasse 2010997 BerlinE Mail: daniel.margulies@gmail.com

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Markworth, SörenMarkworth, SörenMarkworth, SörenMarkworth, SörenMarkworth, SörenNeuroscienceMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössle-Str. 1013125 BerlinTel.: +49 30 9406 2853E Mail: soeren.markworth@mdc-berlin.de

Maslarova, AnnaMaslarova, AnnaMaslarova, AnnaMaslarova, AnnaMaslarova, AnnaExperimental NeurologyCharité, BerlinCharitepl. 110117 BerlinE Mail: anna.maslarova@charite.de

Maziashvil i, NinoMaziashvil i, NinoMaziashvil i, NinoMaziashvil i, NinoMaziashvil i, NinoCharité-Universitätsmedizin, BerlinInstitute for NeurophysiologyTucholskystr. 210117 BerlinTel.: +49 30 450 528376E Mail: nino.maziashvili@charite.de

MergenthalerMergenthalerMergenthalerMergenthalerMergenthaler, Phil ipp, Phil ipp, Phil ipp, Phil ipp, Phil ippExperimentelle NeurologieCharité Universitätsmedizin BerlinCharitéplatz 110117 BerlinTel.: +49 30 450 560149E Mail: philipp.mergenthaler@charite.de

MerklerMerklerMerklerMerklerMerkler, Dr, Dr, Dr, Dr, Dr. Doron. Doron. Doron. Doron. DoronNeuropathologyGeorg-August-UniversityRobert-Koch-Str. 4037075 GöttingenE Mail: merkler@med.uni-goettingen.de

Milenkovic, NevenaMilenkovic, NevenaMilenkovic, NevenaMilenkovic, NevenaMilenkovic, NevenaMax-Delbrück Centrum für molekulare MedizinRobert-Rössle-Str. 1013092 BerlinE Mail: milenkovic@mdc-berlin.de

Misgeld, DrMisgeld, DrMisgeld, DrMisgeld, DrMisgeld, Dr. Thomas. Thomas. Thomas. Thomas. ThomasInstitut für NeurowissenschaftenTechnische Universität MünchenBiedersteiner Str. 2980802 MünchenTel.: +49 89 4140 3512E Mail: thomas.misgeld@lrz.tu-muenchen.de

MüllerMüllerMüllerMüllerMüller, Dr, Dr, Dr, Dr, Dr. Thomas. Thomas. Thomas. Thomas. ThomasMedical GeneticsMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössle-Str. 1013125 BerlinE Mail: thomu@mdc-berlin.de

Nitsch, PNitsch, PNitsch, PNitsch, PNitsch, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. R. R. R. R. RobertobertobertobertobertInstitute for Cell Biology and NeurobiologyCharité-Universitätsmedizin BerlinChariteplatz 110115 BerlinTel.: +49 30 450 528002E Mail: robert.nitsch@charite.de

Nockemann, DinahNockemann, DinahNockemann, DinahNockemann, DinahNockemann, DinahCharitéKlinik für Anästhesiologie und operative IntensivmedizinKrahmerstr. 6-1012207 BerlinTel.: +49 30 844 52131E Mail: dinah.nockemann@charite.de

OffenhauserOffenhauserOffenhauserOffenhauserOffenhauser, Nikolas, Nikolas, Nikolas, Nikolas, NikolasExperimental NeurologyCharite, CCMChariteplatz 110117 BerlinE Mail: nikolas.offenhauser@charite.de

Oliveira Ferreira, Ana IsabelOliveira Ferreira, Ana IsabelOliveira Ferreira, Ana IsabelOliveira Ferreira, Ana IsabelOliveira Ferreira, Ana IsabelExperimental NeurologyCharité University MedicineCharitéplatz 110117 BerlinTel.: +49 30 450 560007E Mail: ana.ferreira@charite.de

Otto, WolfgangOtto, WolfgangOtto, WolfgangOtto, WolfgangOtto, WolfgangCharité, Center for AnatomyInstitute of Cell Biology and NeurobiologyPhilippstr. 1210115 BerlinTel.: +49 30 450 58124E Mail: wolfgang.otto@charite.de

PPPPPark, Su-ark, Su-ark, Su-ark, Su-ark, Su- JinJinJinJinJinInstitut für Medizinische ImmunologieCharité- Universitätsklinikum Berlin, CCMMonbijoustr. 2a10117 BerlinTel.: +49 30 450524195E Mail: su-jin.park@charite.de

Paterka, MagdalenaPaterka, MagdalenaPaterka, MagdalenaPaterka, MagdalenaPaterka, MagdalenaCecilie Vogt Clinic for Neurology in the HKBBCharité - University Medicine Berlin and Max-Delbrück-Centrum für Molekulare MedizinChariteplatz 110117 BerlinTel.: +49 30 450 539051E Mail: magdalena.paterka@charite.de

Patzke, ChristopherPatzke, ChristopherPatzke, ChristopherPatzke, ChristopherPatzke, ChristopherNeuronal Connectivity, AG RathjenMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössle-Str. 1013125 BerlinTel.: +49 30 9406 3304E Mail: cpatzke@mdc-berlin.de

Pehrs, CorinnaPehrs, CorinnaPehrs, CorinnaPehrs, CorinnaPehrs, CorinnaBerlinCharité Campus MitteFehrbellinerstr. 5110119 BerlinTel.: +49 30 1776281365E Mail: corpehrs@gmx.de

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PPPPPeteretereteretereter, Dr, Dr, Dr, Dr, Dr. Jens. Jens. Jens. Jens. Jens-Uwe-Uwe-Uwe-Uwe-UweKlinik für Psychiatrie und PsychotherapieCharité BerlinCharitéplatz 110117 BerlinE Mail: jens-uwe.peter@charite.de

PPPPPeters, Dreters, Dreters, Dreters, Dreters, Dr. med. Oliver. med. Oliver. med. Oliver. med. Oliver. med. OliverDepartment of Psychiatry and Psychotherapy, CBFCharité - University Medicine BerlinEschenallee 314050 BerlinTel.: +49 30 8445 8215E Mail: oliver.peters@charite.de

PfefferPfefferPfefferPfefferPfeffer, Carsten, Carsten, Carsten, Carsten, CarstenPhysiology and Pathology of Ion TransportMax-Delbrück-Centrum for Molecular MedicineRobert-Rössle-Strasse 1013125 BerlinTel.: +49 30 9406 2962E Mail: Carsten.Pfeffer@mdc-berlin.de

PfüllerPfüllerPfüllerPfüllerPfüller, Caspar, Caspar, Caspar, Caspar, CasparCecilie Vogt Clinic for NeurologyCharité University Medicine BerlinCharitéplatz 110117 BerlinE Mail: caspar.pfueller@charite.de

Piehl, Christ ianPiehl, Christ ianPiehl, Christ ianPiehl, Christ ianPiehl, Christ ianLeibniz-Institut für Molekulare PharmakologieRobert-Rössle-Str. 1013125 BerlinE Mail: piehl@fmp-berlin.de

PPPPPina, Drina, Drina, Drina, Drina, Dr. Ana-L. Ana-L. Ana-L. Ana-L. Ana-LuisauisauisauisauisaBerlin Center for Regenerative TherapiesCharite Medical UniversityMonbijoustr 2a, Ida-Simon-Haus 03-01510117 BerlinTel.: +49 30 450 524122E Mail: ana-luisa.pina@charite.de

Pitarokoil i, Kall iopiPitarokoil i, Kall iopiPitarokoil i, Kall iopiPitarokoil i, Kall iopiPitarokoil i, Kall iopiCecilie Vogt Clinic for Neurology in the HKBBCharité - University Medicine Berlin and MDCChariteplatz 110117 BerlinTel.: +49 30 450 539051E Mail: kalliopi.pitarokoili@charite.de

PPPPPoole, Droole, Droole, Droole, Droole, Dr. K. K. K. K. KateateateateateFunction and Dysfunction of the Nervous SystemMax Delbrück Center for Molecular MedicineRobert Rössle Str. 1013125 BerlinTel.: +49 30 9406 3789E Mail: kate.poole@mdc-berlin.de

PPPPPri l lerri l lerri l lerri l lerri l ler, P, P, P, P, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. Josef. Josef. Josef. Josef. JosefNeuropsychiatry, Laboratory of Molecular PsychiatryCharité-Universitätsmedizin BerlinSchumannstr. 20/2110117 BerlinTel.: +49 30 450 517209E Mail: josef.priller@charite.de

Prozorovski, TimProzorovski, TimProzorovski, TimProzorovski, TimProzorovski, TimCharité, Cecilie-Vogt-Klinik für NeurologieCharitéplatz 110117 BerlinE Mail: timour.prozorovski@charite.de

Pusch, KathrinPusch, KathrinPusch, KathrinPusch, KathrinPusch, KathrinGerman Language and LinguisticsHumboldt University of BerlinDorotheenstrasse 2410117 BerlinTel.: +49 30 209 39732E Mail: kathrin.pusch@psychologie.hu-berlin.de

Quinn, MichaelQuinn, MichaelQuinn, MichaelQuinn, MichaelQuinn, MichaelCharite Medical NeuroscienceWeinbergsweg 210119 BerlinE Mail: michael.quinn@charite.de

RRRRRapp, Drapp, Drapp, Drapp, Drapp, Dr. Dr. Dr. Dr. Dr. Dr. Michael. Michael. Michael. Michael. MichaelGeriatric Psychiatry CenterCharité Campus Mitte, Psychiatric University Clinic atSt. Hedwig’s HospitalGrosse Hamburger Str. 5-1110115 BerlinTel.: +49 30 2311 2959E Mail: michael.rapp@charite.de

Rex, AndreRex, AndreRex, AndreRex, AndreRex, AndreInstitute of Pharmacology and ToxicologyFreie Universität BerlinKoserstr. 2014195 BerlinE Mail: a.rex@fu-berlin.de

RRRRReyeseyeseyeseyeseyes -Haro, Dr-Haro, Dr-Haro, Dr-Haro, Dr-Haro, Dr. Daniel. Daniel. Daniel. Daniel. DanielNeurosciencesMax Delbrueck CenterRobert-Roessle-Str. 1013125 BerlinTel.: +49 30 9406 3503E Mail: reyesharo@mdc-berlin.de

RichterRichterRichterRichterRichter, P, P, P, P, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. Angelika. Angelika. Angelika. Angelika. AngelikaDepartment of Pharmacology and ToxicologyFaculty of Veterinary Medicine, FU BerlinKoserstr. 2014195 BerlinE Mail: richtera@zedat.fu-berlin.de

Rieckmann, DrRieckmann, DrRieckmann, DrRieckmann, DrRieckmann, Dr. Nina. Nina. Nina. Nina. NinaPsychiatryCharité Campus MitteCharitéplatz 110117 BerlinE Mail: nina.rieckmann@charite.de

RRRRRosenbergerosenbergerosenbergerosenbergerosenberger, K, K, K, K, KarenarenarenarenarenInstitute for Cell Biology and Neurobiology, Center forAnatomyCharité-Universitätsmedizin BerlinCharitéplatz 110117 BerlinTel.: +49 30 450 528345E Mail: karen.rosenberger@charite.de

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Roth, StephanRoth, StephanRoth, StephanRoth, StephanRoth, StephanNeurowissenschaftliches ForschungszentrumCharité Universitätsmedizin - BerlinCharitéplatz 110117 BerlinTel.: +49 30 450 539041E Mail: stephan.roth@charite.de

Sander-Thömmes, Dr. TilmannAG 8.21Physikalisch-Technische BAAbbestr. 2-1210587 BerlinTel.: +49 30 3481 7436E Mail: tilmann.sander-thoemmes@ptb.de

SandowSandowSandowSandowSandow, Nora, Nora, Nora, Nora, NoraCharité, J. Mueller Institut fuer PhysiologieTucholskystr. 210117 BerlinTel.: +40 30 1723245089E Mail: nora.sandow@charite.de

Santos TSantos TSantos TSantos TSantos Torres, Drorres, Drorres, Drorres, Drorres, Dr. Julio. Julio. Julio. Julio. JulioMolecular NeurobiologyMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössle Strasse 1013125 BerlinE Mail: julio.santostorres@mdc-berlin.de

Scheffel, JörgScheffel, JörgScheffel, JörgScheffel, JörgScheffel, JörgInstitute of NeuropathologyUniversity of GöttingenRobert-Koch-Straße 4037075 GöttingenTel.: +49 551 398 469E Mail: joerg.scheffel@med.uni-goettingen.de

Scheibe, FranziskaScheibe, FranziskaScheibe, FranziskaScheibe, FranziskaScheibe, FranziskaLaboratory for Molecular Psychiatry/ ExperimentalNeurologyCharité - University Medicine BerlinCharitéplatz 110117 BerlinTel.: +49 30 450 560184E Mail: franziska.scheibe@charite.de

Schipke, DrSchipke, DrSchipke, DrSchipke, DrSchipke, Dr. Carola. Carola. Carola. Carola. CarolaDepartment of Psychiatry and Psychotherapy, CBFCharitéKrahmerstr. 6-1012207 BerlinTel.: +49 30 8445 3779/E Mail: carola.schipke@charite.de

Schmidt, DrSchmidt, DrSchmidt, DrSchmidt, DrSchmidt, Dr. Hannes. Hannes. Hannes. Hannes. HannesFG EntwicklungsneurobiologieMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössle-Str.1013092 BerlinE Mail: hannes.schmidt@mdc-berlin.de

Schmidt, SaskiaSchmidt, SaskiaSchmidt, SaskiaSchmidt, SaskiaSchmidt, SaskiaMyologyECRC, ChariteLindenberger Weg 8013125 Berlin

Schmitz, PSchmitz, PSchmitz, PSchmitz, PSchmitz, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. Dietmar. Dietmar. Dietmar. Dietmar. DietmarNeurowissenschaftliches Forschungszentrum (NWFZ)Charité-Universitätsmedizin BerlinCharitéplatz 110117 BerlinTel.: +49 30 450 539054E Mail: dietmar.schmitz@charite.de

Schöwel, DrSchöwel, DrSchöwel, DrSchöwel, DrSchöwel, Dr. V. V. V. V. VerenaerenaerenaerenaerenaMyologyECRC, ChariteLindenberger Weg 8013125 BerlinE Mail: verena.schoewel@charite.de

SchreiberSchreiberSchreiberSchreiberSchreiber, Melanie, Melanie, Melanie, Melanie, MelanieHumboldt UniversityDepartement of PsychologyRudower Chaussee 1812439 BerlinE Mail: Melanie.Schreiber@psychologie.hu-berlin.de

Schubert, DrSchubert, DrSchubert, DrSchubert, DrSchubert, Dr. R. R. R. R. RuthuthuthuthuthAG Neurophysik, Klinik für Neurologie und klinischeNeurophysiologieCharité, Universitätsmedizin Berlin, Campus BenjaminFranklinHindenburgdamm 3012200 BerlinTel.: +49 30 8445 4704E Mail: ruth.schubert@charite.de

Schuermann, BeateSchuermann, BeateSchuermann, BeateSchuermann, BeateSchuermann, BeateClinical PsychologyHumboldt-University of BerlinRudower Chaussee 1810099 BerlinTel.: +49 30 209 39412E Mail: Beate.Schuermann@psychologie.hu-berlin.de

Schulze TSchulze TSchulze TSchulze TSchulze Topphoffopphoffopphoffopphoffopphoff, Ulf, Ulf, Ulf, Ulf, UlfCecilie-Vogt-Klinik für NeurologieCharite Universitätsmedizin Berlin und Max-Delbrück-Centrum für Molekulare MedizinChariteplatz 110117 BerlinE Mail: ulf.topphoff@charite.de

SchweizerSchweizerSchweizerSchweizerSchweizer, Dr, Dr, Dr, Dr, Dr. Ulrich. Ulrich. Ulrich. Ulrich. UlrichNeurobiology of SeleniumCharité-Universitätsmedizin BerlinCharitéplatz 110117 BerlinTel.: +49 30 450 539041E Mail: ulrich.schweizer@charite.de

Seifert, StefanieSeifert, StefanieSeifert, StefanieSeifert, StefanieSeifert, StefanieCellular NeuroscienceMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössle-Str. 1013125 BerlinTel.: +49 30 9406 3723E Mail: s.seifert@mdc-berlin.de

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of the SFB 507Address ListAddress ListAddress ListAddress ListAddress List

Schmitz, PSchmitz, PSchmitz, PSchmitz, PSchmitz, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. Dietmar. Dietmar. Dietmar. Dietmar. DietmarNeurowissenschaftliches Forschungszentrum (NWFZ)Charité-Universitätsmedizin BerlinCharitéplatz 110117 BerlinTel.: +49 30 450 539054E Mail: dietmar.schmitz@charite.de

Schöwel, DrSchöwel, DrSchöwel, DrSchöwel, DrSchöwel, Dr. V. V. V. V. VerenaerenaerenaerenaerenaMyologyECRC, ChariteLindenberger Weg 8013125 BerlinE Mail: verena.schoewel@charite.de

SchreiberSchreiberSchreiberSchreiberSchreiber, Melanie, Melanie, Melanie, Melanie, MelanieHumboldt UniversityDepartement of PsychologyRudower Chaussee 1812439 BerlinE Mail: Melanie.Schreiber@psychologie.hu-berlin.de

Schubert, DrSchubert, DrSchubert, DrSchubert, DrSchubert, Dr. R. R. R. R. RuthuthuthuthuthAG Neurophysik, Klinik für Neurologie und klinischeNeurophysiologieCharité, Universitätsmedizin Berlin, Campus BenjaminFranklinHindenburgdamm 3012200 BerlinTel.: +49 30 8445 4704E Mail: ruth.schubert@charite.de

Schuermann, BeateSchuermann, BeateSchuermann, BeateSchuermann, BeateSchuermann, BeateClinical PsychologyHumboldt-University of BerlinRudower Chaussee 1810099 BerlinTel.: +49 30 209 39412E Mail: Beate.Schuermann@psychologie.hu-berlin.de

Schulze TSchulze TSchulze TSchulze TSchulze Topphoffopphoffopphoffopphoffopphoff, Ulf, Ulf, Ulf, Ulf, UlfCecilie-Vogt-Klinik für NeurologieCharite Universitätsmedizin Berlin und Max-Delbrück-Centrum für Molekulare MedizinChariteplatz 110117 BerlinE Mail: ulf.topphoff@charite.de

SchweizerSchweizerSchweizerSchweizerSchweizer, Dr, Dr, Dr, Dr, Dr. Ulrich. Ulrich. Ulrich. Ulrich. UlrichNeurobiology of SeleniumCharité-Universitätsmedizin BerlinCharitéplatz 110117 BerlinTel.: +49 30 450 539041E Mail: ulrich.schweizer@charite.de

Seifert, StefanieSeifert, StefanieSeifert, StefanieSeifert, StefanieSeifert, StefanieCellular NeuroscienceMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössle-Str. 1013125 BerlinTel.: +49 30 9406 3723E Mail: s.seifert@mdc-berlin.de

Seja, PatriciaSeja, PatriciaSeja, PatriciaSeja, PatriciaSeja, PatriciaMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössle-Str. 1013125 BerlinE Mail: patricia.seja@mdc-berlin.de

Siffr in, DrSiffr in, DrSiffr in, DrSiffr in, DrSiffr in, Dr. V. V. V. V. VolkerolkerolkerolkerolkerCecilie-Vogt-Klinik für NeurologieCharité - Universitätsmedizin Berlin und Max-Delbrück-Centrum für Molekulare MedizinCharitéplatz 110117 BerlinTel.: +49 30 4505 39055E Mail: volker.siffrin@charite.de

Sivasubramaniam, Anantha KrishnaSivasubramaniam, Anantha KrishnaSivasubramaniam, Anantha KrishnaSivasubramaniam, Anantha KrishnaSivasubramaniam, Anantha KrishnaMedical NeuroscienceChariteCoppistr. 1410635 BerlinE Mail: anand987@yahoo.com

Slimak, Marta AnnaSlimak, Marta AnnaSlimak, Marta AnnaSlimak, Marta AnnaSlimak, Marta AnnaMolecular NeurobiologyMax-Delbrück-Center for Molecular MedicineRobert-Rössle-Str. 1013092 BerlinE Mail: marta.slimak@mdc-berlin.de

Smith, EwanSmith, EwanSmith, EwanSmith, EwanSmith, EwanNeuroscienceMax Delbrück Center for Molecular MedicineRobert-Rössle-Str. 1013125 BerlinE Mail: ewan.smith@mdc-berlin.de

Soriguera Farrés, AnnaSoriguera Farrés, AnnaSoriguera Farrés, AnnaSoriguera Farrés, AnnaSoriguera Farrés, AnnaPRG Research GroupCharité, Center for Cell Biology and NeurobiologyPhilippstr. 1210115 BerlinTel.: +49 30 450 528031E Mail: anna.soriguera@charite.de

Spahn, ViolaSpahn, ViolaSpahn, ViolaSpahn, ViolaSpahn, ViolaKlinik für Anästhesiologie und operative IntensivmedizinCharité, CBFHindenburgdamm 3012200 BerlinTel.: +49 30 8445 2131E Mail: viola.spahn@charite.de

Spitzmaul, DrSpitzmaul, DrSpitzmaul, DrSpitzmaul, DrSpitzmaul, Dr. Guillermo. Guillermo. Guillermo. Guillermo. GuillermoFMP/Max-Delbrück-Centrum für Molekulare MedizinRobert-Rössle Straße 1013125 BerlinTel.: +49 30 9406 2967E Mail: guillermo.spitzamul@mdc-berlin.de

StadlerStadlerStadlerStadlerStadler, K, K, K, K, KonstantinonstantinonstantinonstantinonstantinCenter for Anatomy, Institute of Cell Biology andNeurobiologyCharité Universitätsmedizin BerlinPhilippstr. 1210115 BerlinTel.: +49 30 450 528027E Mail: konstantin.stadler@charite.de

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VVVVVogt, Drogt, Drogt, Drogt, Drogt, Dr. Johannes. Johannes. Johannes. Johannes. JohannesInstitute of Cell Biology and NeurobiologyCenter for AnatomyCharitéplatz 110115 BerlinTel.: +49 30 450 528429E Mail: johannes.vogt@charite.de

Voitcu, RoxanaVoitcu, RoxanaVoitcu, RoxanaVoitcu, RoxanaVoitcu, RoxanaCharité - Universitätsmedizin BerlinE Mail: r.voitcu@gmail.com

von Heimendahl, Drvon Heimendahl, Drvon Heimendahl, Drvon Heimendahl, Drvon Heimendahl, Dr. Moritz. Moritz. Moritz. Moritz. MoritzBernstein Center for Computational NeuroscienceHumboldt Universität zu BerlinPhilippstr 13, Haus 610115 BerlinTel.: +49 30 209 36350E Mail: moritz.vonheimendahl@bccn-berlin.de

WWWWWende, Drende, Drende, Drende, Drende, Dr. Hagen. Hagen. Hagen. Hagen. HagenMouse GeneticsMax Delbrück Centrum für Molekulare MedizinRobert Rössle Str. 1013125 BerlinTel.: +49 30 9406 3160E Mail: hagen.wende@mdc-berlin.de

WWWWWerrerrerrerrerr, Johannes, Johannes, Johannes, Johannes, JohannesDunckerstr. 1510437 BerlinTel.: +49 174 5604526E Mail: johannes.werr@charite.de

WWWWWichmann, Pichmann, Pichmann, Pichmann, Pichmann, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. F. F. F. F. FelixelixelixelixelixModellierung Kognitiver ProzesseTU BerlinFranklinstr. 28/2910587 BerlinTel.: +49 30 314 73557E Mail: felix.wichmann@tu-berlin.de

Winkelmann, AnnetteWinkelmann, AnnetteWinkelmann, AnnetteWinkelmann, AnnetteWinkelmann, AnnetteBerlin School of Mind and BrainHumboldt-Universität zu BerlinUnter den Linden 610099 BerlinTel.: +49 30 2093 1706E Mail: annette.winkelmann@uv.hu-berlin.de

Wirth, Eva KatrinWirth, Eva KatrinWirth, Eva KatrinWirth, Eva KatrinWirth, Eva KatrinInstitute for Experimental Endocrinology andNeuroscience Research CenterCharitéChariteplatz 110117 BerlinE Mail: eva.wirth@charite.de

Xu, KeXu, KeXu, KeXu, KeXu, KePharmacology, Physiology; TherapeuticsUniv. of North Dakota School of Medicine &amp;Health Sciences501 N Columbia Rd,58203 Grand Forks, North Dakota (U.S.A.)Tel.: +1 218 791 3519E Mail: ke.xu@und.edu

SteinerSteinerSteinerSteinerSteiner, L, L, L, L, LutzutzutzutzutzMedical NeurosciencesCharité - Universitätsmedizin BerlinCharitéplatz 110117 BerlinTel.: +49 30 450 560226E Mail: lutz.steiner@charite.de

Stonkute, AgneStonkute, AgneStonkute, AgneStonkute, AgneStonkute, AgneDevelopmental NeurobiologyMax-Delbrueck-Center for Molecular MedicineRobert-Roessle Str. 1013092 BerlinE Mail: stonkute@mdc-berlin.de

Strauss, DrStrauss, DrStrauss, DrStrauss, DrStrauss, Dr. Ulf. Ulf. Ulf. Ulf. UlfInstitute for Cell and NeurobiologyCharite Universitätsmedizin BerlinChariteplatz 110117 BerlinTel.: +49 30 450 528027E Mail: ulf.strauss@charite.de

StürzebecherStürzebecherStürzebecherStürzebecherStürzebecher, Annika, Annika, Annika, Annika, AnnikaMolecular NeurobiologyMax-Delbrück CentrumRobert-Rössle-Str 1013125 BerlinE Mail: annika.stuerzebecher@mdc-berlin.de

TTTTTeßmann, Grietjeeßmann, Grietjeeßmann, Grietjeeßmann, Grietjeeßmann, GrietjeCellular NeuroscienceMax-Delbrück-Centrum für Molekulare MedizinRobert-Rössle-Straße 1013125 BerlinTel.: +49 30 9406 3723E Mail: grietje.tessmann@mdc-berlin.de

TTTTTrimbuch, Thorstenrimbuch, Thorstenrimbuch, Thorstenrimbuch, Thorstenrimbuch, ThorstenInstitute of Cell- and NeurobiologyCharitePhilippstr.1210115 BerlinE Mail: thorsten.trimbuch@charite.de

Usnich, TUsnich, TUsnich, TUsnich, TUsnich, TatianaatianaatianaatianaatianaCharité - Universitätsmedizin BerlinSiegmunds Hof 2-410555 BerlinTel.: +49 1577 38 70 50E Mail: tatiana.usnich@charite.de

PPPPProfrofrofrofrof. Dr. Dr. Dr. Dr. Dr. P. P. P. P. Peter Veter Veter Veter Veter VajkoczyajkoczyajkoczyajkoczyajkoczyNeurochirurgieCharité Universitätsmedizin BerlinAm Augustenburger Platz 113353 BerlinTel.: +49 30 4505 60002E Mail: peter.vajkoczy@charite.de

VVVVVelmans, Telmans, Telmans, Telmans, Telmans, TanjaanjaanjaanjaanjaInstitute for Cell Biology and NeurobiologyCharité – UniversitätsmedizinCharitéplatz 110117 BerlinTel.: +49 30 4505 28397E Mail: Tanja.Velmans@charite.de

104 BNF2008

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of the SFB 507ZhivkovZhivkovZhivkovZhivkovZhivkov, Zhivko, Zhivko, Zhivko, Zhivko, ZhivkoInstitute for Biology, Aquatic Bioacoustics LaboratoryHumboldt Universität BerlinInvalidenstr. 4310115 BerlinTel.: +49 30 209 38491E Mail: jivkov@gmx.de

Zipp, PZipp, PZipp, PZipp, PZipp, Profrofrofrofrof. Dr. Dr. Dr. Dr. Dr. med. F. med. F. med. F. med. F. med. FraukeraukeraukeraukeraukeCecilie-Vogt-Klinik für Neurologie im HKBBCharité - Universitätsmedizin BerlinCharitéplatz 110117 BerlinTel.: +49 30 4505 39028E Mail: christine.kutschbach@charite.de

ZonnurZonnurZonnurZonnurZonnur, Sarah, Sarah, Sarah, Sarah, SarahCenter for AnatomyCharitéPhilippstr. 1210115 BerlinTel.: +49 30 450 528269E Mail: sarah.zonnur@charite.de