Centre For Neuroscience Indian Institute Of Science
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Centre For Neuroscience Indian Institute Of Science Profile
Transcript of Centre For Neuroscience Indian Institute Of Science
Centre For NeuroscienceIndian Institute Of ScienceProfile
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Overview 3
Research Approaches 4
PhD Program 5
Faculty Profiles 10
Events @ CNS 32
Contents
Understanding the brain is one of the great challenges in modern science. It isa prerequisite and a necessity if we are to diagnose, treat and cure braindisorders that now constitute a huge burden on modern society, including indeveloping countries.
The Centre for Neuroscience (CNS) was established in 2009 in the centenaryyear of IISc with the goal of pursuing research towards understanding thestructure, function and development of the brain in health and disease. Thisrequires studying the brain across different levels of organization usingmolecular, cellular, systems, behavioural and computational approaches. Thediversity of these approaches is also reflected in the varied academicbackgrounds of the faculty at CNS, many of whom have their undergraduatetraining in areas such as Engineering, Physics and Chemistry and Biology. Weanticipate that such diversity is not only critical if we are to understand brainfunction but also provides a stimulating research environment for ourstudents, who we anticipate, will imbibe the interdisciplinary ethos essentialto neuroscience research.
In keeping with this vision, the primary faculty perform cutting edgeinvestigator driven research at different scales using different approaches andmodel systems ranging from invertebrates such as C. elegans, to rodents, tonon-human primates as well as human subjects and patients. Currently theCentre has 9 core faculty. In the next 5 years, the Centre hopes to build on thistradition and recruit faculty with diverse expertise across the broad disciplineof neuroscience. In addition to investigator driven research, the faculty alsoleverage the expertise of researchers in other departments both within andbeyond the institute to address highly complex problems and interdisciplinaryquestions in neuroscience that lie at the interface of clinical research,engineering and other areas of biology. In summary, the Centre is a relativelyyoung initiative that is still in its growing years and has still many paths totraverse. One can certainly hope that with such a vibrant interdisciplinary andcollaborative effort, research at the Centre for Neuroscience will contribute ina meaningful way to brain research in the years ahead.
Overview
Genetics Neural NetworksBehaviour Computational Modelling Neurons
Action Potentials Neural Development Synapse NeuroanatomyHistology Receptors Neurotransmitters Attention Emotion
Vision Cell Biology Neurochemistry Imaging MRI Parkinsons Disease
Alzheimers Disease Electrophysiology Attention Decision-Making
Hippocampus Motor Control Neural Circuits Axonal Regeneration Multi
Photon Imaging Genetic Engineering Neuronal Stem Cells OptogeneticsNeuropharmacology Gene Regulation Signal Processing Decisions AstrocytesSignal Transduction Neural Development CortexSignal Processing Psychophysics
Neurophysiology MicroscopyNeural CodingOscillationsSynapses
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Transgenic and knockout mice and genome editing
In-vivo imaging of neural networks
Live cell imaging
Single molecule tracking using super-resolution microscopy
Nanoscale Organization and Regulation of Post-Synaptic Density
Animal cognition & behavior
Primate neurophysiology (single unit recordings, arrays, microstimulation, behaviour)
Human cognitive neuroscience (behaviour, fMRI, EEG, TMS, tDCS)
Research Approaches
EquipmentMulti-photon microscope based in-vivo imaging system with sub-cellular resolution
Two-photon microscope for live cell imaging
Live cell super resolution imaging with PALM and STORM microscopes
Inverted and upright Apotome and high-speed single molecule imaging
Virus generation and purification facility
Histology facility with cryostat, vibratome and microtome PCR facility with RT-PCR
Small animal behaviour monitoring and experimentation facility
Neurolucida based software tools for tracking and tracing neurons
Single cell electrophysiology
Eye tracker
fMRI compatible EEG and TMS
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PhD Program At CNS
Students at CNS are exposed to cutting edgeneuroscience research through the CNS faculty,whose interests span the gamut frommolecular to systems and cognitiveneuroscience. Research at CNS is highlyinterdisciplinary and reflects the diversebackgrounds of the faculty themselves. Thedepartment offers world class facilities andequipment together with a vibrant environmentfor research that consists of journal clubs andseminars. The department conducts nationallevel and international level workshopsregularly, where students get to interact withthe best neuroscientists from India and abroad.As part of their PhD experience students arealso given opportunities to travel to nationaland internal conferences to present theirresearch.
The CNS PhD program is designed to provide asolid foundation of neuro-science to all studentsincluding those that do not have any priorbackground/experience in neuroscience.Incoming first year PhD students are not pre-assigned to an advisor but are instead askedto take the entire first semester to decide on thelaboratory that they wish to join for their PhD.They are encouraged to talk to the facultyand students in each laboratory and also do arotation in order to make an informed decision.
In addition, students take courses on molecularand systems neuro- science in the first semesterand advanced readings and grant writing in thesecond semester, together with relevant coursesoffered by other departments.
This approach helps them to understandand provides them an opportunity tocarry out neuroscience research in thearea that interests them the most. Thestudents make the final choice of theirthesis advisor/laboratory by the end ofthe first semester. During the second semesterstudents are expected to chooseone of two advanced neurosciencecourses either in systems and cognitiveneuroscience or in molecular and cellularneuroscience, where they get exposed to thelatest research in the field through reading anddiscussion of relevant research papers, learn tomake presentations and generate original ideasunder the guidance of the course supervisors.
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PhD students are required to take a total of12 credits of coursework. Courses at IISc arerigorous and research oriented and emphasizeunderstanding fundamentals rather than rotememory. At the end of their second year, PhDstudents are required to pass acomprehensive exam in which they are testedon their understanding of their coursefundamentals as well as their research progressin the two years. They are also required topresent their work on an annual basis in theform of a seminar.
PhD students are provided with a monthlystipend (as per institute norms) and with
accommodation in the student hostels at IISc.Campus life at IISc is extremely vibrant with abroad spectrum of cultural and sports activities.
For more details about the admissions processfor both PhD and integrated PhD programmesplease see
https://admissions.iisc.ac.in
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Faculty Profiles
I received my B.Tech from the Indian Institute of Technology (Bombay),
and MS and PhD from Johns Hopkins University, all in Electrical
Engineering. I completed my postdoctoral research at Carnegie Mellon
University and then joined IISc. I am fascinated by how the brain
transforms sensory information into perception.
S.P. ArunAssociate Professor
T: +91 80 2293 3436
1. Agrawal A, Hari KVS & Arun SP(2019) Reading increases thecompositionality of visual wordrepresentations. PsychologicalScience, in press.
2. Ratan Murty NA & Arun SP (2018)Multiplicative mixing of objectidentity and image attributes insingle inferior temporal neurons.Proceedings of the NationalAcademy of Sciences (USA).115:E3276-85.
3. Pramod RT & Arun SP (2018)Symmetric objects becomespecial in perception due togeneric computations inneurons. Psychological Science,29:95-109.
4. Ratan Murty NA & Arun SP (2017)Seeing a straight line on a curvedsurface: Decoupling of patternsfrom surfaces by single ITneurons. Journal ofNeurophysiology. 117: 104-116.
5. Pramod RT and Arun SP (2016)Object attributes combineadditively in visual search.Journal of Vision.16(8):1-29.
6. Zhivago KA and Arun SP (2016)Selective IT neurons are selectivealong many dimensions. Journalof Neurophysiology. 115:1512-1520.
Selected Publications:
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We recognize objects easily every day, but objectrecognition is in fact a very difficult problem.Even leading computer algorithms do not matchhuman performance today. Object recognition isnot easy for the brain either: a series of corticalareas, taking up ~40% of the brain, is dedicatedto vision. But we know very little about the rulesby which the brain transforms what we see intowhat we perceive. What is the nature of thisrepresentation? What are the underlying rules?
ApproachOur approach to this problem is best understoodthrough an analogy to colour. We see millions ofcolours but it is well known that colourperception is three-dimensional. Any colour weperceive can be represented using threenumbers. Can we do likewise for the millions ofshapes we see? Do shapes also reside in a low-dimensional space?To gain insight into these questions, we performbehavioural and imaging experiments inhumans and record the electrical activity of
neurons from monkey visual cortex.
In the human experiments, we probe theunderlying perceptual representationusing behavioural tasks such as visual searchor categorization and investigate the underlyingrepresentation using fMRI and TMS. In themonkey experiments, we probe therepresentation at the level of single neurons inthe inferotemporal cortex, an area critical forobject recognition. We work with these diversetypes of data to build, test and validatecomputational models of object recognition.
For more informationVision Lab IISc
Dynamics of 3D view invariance in a single IT neuron.Responses of a single IT neuron are shown to a trumpet and amotorbike at multiple views. Each row represents a trial, andticks represent the times of action potentials produced by theneuron. IT neurons show a gradual development of viewpointinvariance over response.
From Ratan Murty & Arun (2015)
Object Recognition
Reading expertise reduces adjacent letterinteractions, making words more discriminable. ATelugu reader looking at Telugu (magenta) andMalayalam (cyan) letter strings perceives Telugu lettersas further apart, allowing for easier parsing. Likewise aMalayalam reader perceives Malayalam letters to befurther apart. These changes in visual processingmatched best with an object-selective region (LO) in thebrain.
From Agrawal, Hari & Arun, 2019
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Selected Publications: I graduated with a PhD in developmental biology from the Institute of
Molecular and Cell Biology (IMCB-A*STAR) that was part of The National
University of Singapore. My PhD work was conducted in with Professor
Bill Chia laboratory in Singapore and King’s College, London. I then
joined the laboratory of Professor Josh Kaplan as a postdoctoral fellow
at the Department of Molecular Biology, Massachusetts General
Hospital, Boston, USA. Upon completion of my postdoctoral training, I
started my own laboratory as an Assistant Professor at Indian Institute of
Science Education and Research (IISER), Mohali, India. In May 2019, I
moved to the Centre for Neuroscience.
1. Tikiyani V, Li L, Sharma P, Liu H, HuZ and Babu K (2018) Wnt isregulated by the tetraspan proteinHIC-1 through its interaction withNeurabin/NAB-1. Cell Reports. 25(7):1856-71.
2. Sharma P*, Li L*, Liu H, Tikiyani V, HuZ© and Babu K© (2018)The Claudin-like protein, HPO-30, is required tomaintain LAChRs at theCaenorhabditis elegansneuromuscular junction. Journal ofNeuroscience. 38(32): 7072-87.
3. Bhardwaj A*, Thapliyal S*, Dahiya Yand Babu K (2018) FLP-18 functionsthrough the G-protein coupledreceptors NPR-1 and NPR-4 tomodulate reversal length inCaenorhabditis elegans. Journal ofNeuroscience. 38(20):4641-54.
4. Thapliyal S, Vasudevan A*, Dong Y*,Bai J, Koushika SP and Babu K (2018)The C-terminal of CASY-1/Calsyntenin regulatesGABAergic synaptic transmission atthe Caenorhabditis elegansneuromuscular junction. PLoSGenetics. 14(3): e1007236.
5. Pandey P, Bhardwaj A and Babu K(2017) Regulation of WNT Signalingat the Neuromuscular Junction bythe Immunoglobulin Super-FamilyProtein RIG-3 in Caenorhabditiselegans. Genetics. 206(3): 1521- 34.
Kavita BabuAssociate Professor
T:+91 80 2293 2062
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Molecules And MechanismsUnderlying Synaptic Function
Unlike our brain that has billions of neurons andtrillions of synapses, the free-living nematodeCaenorhabditis elegans has 302 neurons andaround 7000 synapses. Our laboratory isinterested in understanding two fundamentalquestions in synaptic biology:
1. How do a class of tetra span protein calledclaudins function in neurons and synapses?To address this question we are looking ataspects of neuronal and synapticdevelopment and function in claudinmutants and are looking at the expressionpattern of claudins at the synapse. Our recentwork has implicated two C. elegans claudinsin maintaining normal levels of postsynapticreceptors at the neuromuscular junction.
2. We are also interested in understandingmolecules and mechanisms underlyingnormal locomotory behavior in C. elegans.More specifically we want to find out howsmall peptides (neuropeptides) that are sentout by one neuron affect the same and/orneighboring neurons and how this action byneuropeptides and their receptors affectslocomotion.
Image : Mutants in a claudin show areduction in acetylcholine receptor levels(red) at the neuromuscular junction. Thebody-wall muscles are marked in green.Image from Sharma P., Lei L., et al; 2018 andimage courtesy Pallavi Sharma.
Our laboratory uses genetics, imagingtechniques including neuronal imaging,FRAP, optogenetic experiments,electrophysiological recordings and celland molecular biology techniquesincluding CRISPR-Cas9 and RNAi to betterunderstand the molecular mechanismsunderlying neuronal and synapticfunction.
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Sridharan DevarajanAssistant Professor
T: +91 80 2293 3434
I obtained my Bachelors and Masters (Dual) engineering degrees from the
Indian Institute of Technology (IIT) Madras. As a Smith Graduate Fellow at
Stanford University, I studied the dynamics of attention-related brain
networks using functional neuroimaging. I completed my PhD
investigating the role of the midbrain in selective attention, with a
combination of in-vivo and in-vitro electrophysiology (with Prof. Eric
Knudsen) and neuromorphic modeling (with Prof. Kwabena Boahen). As a
Dean’s Postdoctoral Fellow at Stanford, I developed neurobehavioral
models for attention and decision-making.
As an Assistant Professor and Wellcome Trust DBT India Alliance
Fellow, I lead the Cognition Lab at the Centre for Neuroscience at IISc, Our
lab studies the brain basis of attention and decision-making behaviors
with a focus on neural computations underlying cognition.
1. Banerjee S, Grover S, GaneshS, Sridharan D (2019) Sensory anddecisional components ofendogenous attention aredissociable. Journalof Neurophysiology, in press.
2. Sagar V, Sengupta R, Sridharan D(2019) Dissociable sensitivity andbias mechanisms mediatebehavioral effects of exogenousattention. Scientific Reports.9:12657.
3. Sreenivasan V, Sridharan D (2019)Subcortical connectivity correlates selectively with attention's effectson spatial choice bias. Proceedingsof the National Academy ofSciences, USA. 116(39):19711-19716.
4. Kumar S, Sreenivasan V, Talukdar P,Pestilli, F, Sridharan D (2019) ReAl-LiFE: Accelerating the discovery ofindividualized brain connectomeson GPUs. In proceedings of the33rd AAAI Conference on ArtificialIntelligence. 33:630-638.
5. Sridharan D, Steinmetz N, MooreT, Knudsen EI (2017) Does thesuperior colliculus controlperceptual sensitivity or choice biasduring attention? Evidence from amulti-alternative decisionframework. Journal ofNeuroscience. 37(3):480-511.
Selected Publications:
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How does our brain enable us to pay attentionselectively to certain important objects in theworld, and to ignore other, irrelevant ones? Whathappens in the brain when we make importantdecisions? Our research focuses onunderstanding the neural basis of cognitivephenomena such as perception, selectiveattention and decision-making. We seek toidentify key mechanisms by which specificbrain regions and neural oscillationscontribute to these phenomena in humans. Inorder to accomplish this goal, we pursuea highly inter disciplinary approach.
First, we measure and analyze brain activityas subjects perform attention-demanding tasksinvolving complex decisions. Forthis, we employ state-of-the-art techniques suchas functional magnetic resonance imaging(fMRI), electrophysiology (EEG) and machine-learning. Second, we quantify and visualizestructural and functional connectivity in thebrain using emerging techniques such asdiffusion MRI and Granger causality.
These techniques also help us identifyabnormalities in connectivity patterns in patientswith cognitive disorders. Third, we investigatehow specific brain regions contribute toattention and decision-making using non-invasive neuro-stimulation techniques, such astranscranial electrical and magnetic stimulation,(tES/ tMS). Finally, we seek to simultaneouslyperturb and record neural activity in the brainwith combinations of brain stimulation andrecording technologies such as interleaved fMRI-tMS and simultaneous EEG-tES.
A strategic combination of these techniques,along with quantitative analysis of behavior, hasthe potential to significantly advance ourunderstanding of how cognitive phenomenaemerge in the human brain and how they shapebehavior.
Goals:• Investigating how brain networks interact during attention and decision-making with neuroimaging.• Identifying differences in connectivity between healthy and diseased brains with diffusion imaging.• Identifying the causal role of brain regions in cognition with transcranial neurostimulation.• Linking brain and behaviour with theoretical and computational models.
Neural ComputationsUnderlying Cognition
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I did my undergraduate training at Jamal Mohammad College of
Bharathisadan University, Trichy, where I obtained both my Bachelors and
Masters Degrees. After my undergraduate training, I joined Prof. Sudipta
Maiti at the Tata Institute of Fundamental Research for doctoral research
where I developed several optical tools to follow the release dynamics and
sequestration of serotonin using its native fluorescence in live neurons. For
my post-doctoral training, I worked with Prof. Timothy Ryan at Weil Cornell
Medical College of Cornell University, New York and later with Prof. Alcino
Silva at the David Griffin School of Medicine, UCLA.
1. A Singh, S Kumar, VP Singh, A Das, JBalaji (2017) Flavor DependentRetention of Remote Food PreferenceMemory. Frontiers in BehavioralNeuroscience. 11:7.
2. Singh A and J Balaji (2017) SensitiveEstimation of Flavor Preferences inSTFP Using Cumulative Time Profiles.Bio-protocol. Vol 7.
3. Kumar S, Singh A, Singh VR, George JBand Balaji J (2016) SaturationDynamics Measures Absolute CrossSection and Generates Contrastwithin a Neuron. Biophysical Journal.111, 1328–1336.
4. Rogerson T, Balaji J, Cai DJ, Sano Y,Lee Y-S, Zhou Y, Bekal P, Deisseroth K& Silva AJ (2016) Molecular andCellular Mechanisms for Trapping andActivating Emotional Memories. PlosOne. 11(8), e0161655.
5. Singh HJ, Singh VR, Sikdar SK, Balaji J& Ghosh A (2016) Circular DifferentialTwo-Photon Luminescence fromHelically Arranged PlasmonicNanoparticles. ACS Photonics. 3, 863–868.
Selected Publications:
Balaji JayaprakashAssistant Professor
T: +91 80 2293 3049
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Left: Neurons of the mice brain obtained from Thy-1 GFP miceRight: High resolution in vivo images of dendrites clearly showing the dendritic spines.
Neurobiology Of Learning And Memory
Research in our lab is focused onunderstanding how memories of past eventsinfluence the acquisition of new memory andexperiences. Using mice as a model system, wefollow the neuronal correlates of memory. Wefollow changes accompanying acquisition,formation and retrieval of memory through in-vivo two-photon imaging Longitudinal imagingof the same mice over the entire process ofmemory consolidation provides us a uniqueability to watch, follow and study theseprocesses as they happen. We combine thisability with small animal behaviour andmolecular genetics to investigate:
i) How the internal representation of remoteevents (events that happened a long timeago) that are similar in nature but distinct incontent are encoded.
ii) When such events are encoded intwo (NMDAR dependent and NMDARindependent) molecularlyindependent pathways, how do theircorresponding internal representationschange at cellular and synaptic scale?
iii)How multiple memories interact with eachother and influence future behaviour.
iv)What happens to temporal information insuch representations of old memories.
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My undergraduate training was at St. Xavier’s College, Mumbai and
Bombay University, where I obtained my Bachelors and Masters degrees,
respectively. My doctoral training was with Dr. Allen Humphrey in the
Department of Neurobiology at the University of Pittsburgh where I
examined the neural mechanisms involved in the processing of motion in
the visual system. For my postdoctoral training, I worked with Dr. Jeffrey
Schall at Vanderbilt University studying the primate visuomotor system to
more directly relate neural activity to psychological functions and
behaviour.
Aditya MurthyProfessor and Chair
T: +91 80 2293 3290
1. Venkataramani PV and Murthy A(2018) Distinct mechanisms explainthe control of reach speed planning:evidence from a race modelframework. Journal ofNeurophysiology.120(3):1293-1306.
2. Sendnilnathan N., Basu D.and Murthy A (2017) Simultaneousanalysis of the LFP and spikingactivity reveals essentialcomponents of a visuomotortransformation in the frontal eyefield. Proceedings of the NationalAcademy of Sciences, (USA). 114(24) 6370-6375.
3. Jana Sumitash, Gopal Atul PA.and Murthy A (2017) Evidence ofcommon and separate eye andhand accumulators underlyingflexible eye-hand coordination.Journal of Neurophysiology.117(1):348-364.
4. Singh P., Jana S., Ghosal A.and Murthy A (2016) Exploration ofjoint redundancy but not task spacevariability facilitates supervisedmotor learning. Proceedings of theNational Academy of Sciences,(USA). 113(50):14414-19.
5. Bhutani N., SureshbabuRamakrishnan, A. A. Farooqui, M.Behari, V. Goyal, and Murthy A(2013) Queuing of concurrentmovement plans by basal ganglia.Journal of Neuroscience. 33(24):9985-97.
Selected Publications:
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Motor Control
Motor learning in the presence of a force field
Stimulation of parietal cortex during
a reaching task
VISUO-MOTOR CONTROL IS STUDIED AT DIFFERENT LEVELS
BEHAVIOUR NETWORKS SINGLE NEURONS
Activity of a neuron in a memory-guided saccade task
-400 1000 16000
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Ne
ura
l a
cti
vity
(sp
ike
s/s)
Time from target onset (ms)0Target markers
Saccade markers
The brain is the most complex informationprocessing systems known to man andconsiderable neural machinery is devoted tomaking visuo-motor tasks such as reaching andgrasping seem effortless. Drawing from researchin robotics, many steps are likely to be involvedwhile planning and executing movements. Someof these stages are decision-making or targetselection, coordinate transformations, planningkinematics and dynamics, error correction andperformance monitoring. While movements inrobots can be superior to naturally occurringmovements in terms of speed and accuracy, theyare still relatively primitive when it comes tomimicking natural behaviours that occur inunpredictable and unstructured environments.Our lab studies the neural and computationalbasis of movement planning and control with anemphasis to understand the basis of flexibilityand control that is the hallmarkof intelligent action.
From the perspective of behaviour we seek tounderstand the nature of computations thatenable motor control; from the perspective ofthe brain we seek to understand the contributionof circumscribed neural circuits to motorbehaviour; and by recording the electrical activityof neurons and muscles we seek to understandhow such computational processes areimplemented by the brain. Our research interestsspan the fields of visual perception, decision-making, and the generation of motor behaviourand involve the application ofcognitive/psychophysical, neuro psychologicaland electrophysiological techniques in humanand non-human primates. We anticipate that inthe long term this work will be useful tounderstand the basis of different motor disordersand develop brain machine interface systemsthat are only beginning to be exploited asengineering and brain sciences are starting toincreasingly interface.
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Deepak NairAssistant Professor
T: +91 80 2293 3535
I completed my Masters in Physics at IIT Madras, Chennai before moving to
Leibniz Institute for Neurobiology (LIN) in Magdeburg, Germany for my
PhD. After my PhD, I moved to Bordeaux, France to pursue my post-
doctoral research with Dr. Daniel Choquet. There I used state-of-the-art
single molecule microscope techniques to study the localization and
movement of synaptic molecules at the nanoscale.
Selected Publications:
1. Nanguneri S, Pramod RT, Efimova N,Das D, Jose M, Svitkina T, and Nair,D (2019) Characterization ofnanoscale organization of F-actin inmorphologically distinct dendriticspines in vitro using supervisedlearning. eNeuro 6.
2. Venkatachalapathy, M., Belapurkar,V, Jose, M, Gautier, A, and Nair, D(2019) Live cell super resolutionimaging by radial fluctuations usingfluorogen binding tags. Nanoscale.11, 3626-3632
3. Kommaddi, R.P., Das, D.,Karunakaran, S., Nanguneri, S.,Bapat, D., Ray, A., Shaw, E., Bennett,D.A., Nair, D and Ravindranath, V(2018) Aβ mediates F-actindisassembly in dendritic spinesleading to cognitive deficits inAlzheimer's disease. Journal ofNeuroscience. 38, 1085-1099.
4. Harper, C.B., Papadopulos, A., Martin,S., Matthews, D.R., Morgan, G.P.,Nguyen, T.H., Wang, T., Nair, D.,Choquet, D., and Meunier, F.A.(2016) Botulinum neurotoxin type-Aenters a non-recycling pool ofsynaptic vesicles.Scientific reports. 6, 19654
5. Widera, D., Klenke, C., Nair, D.,Heidbreder, M., Malkusch, S.,Sibarita, J.-B., Choquet, D.,Kaltschmidt, B., Heilemann, M., andKaltschmidt, C (2016) Single-particletracking uncovers dynamics ofglutamate-induced retrogradetransport of NF-κB p65 in livingneurons. Neurophotonics. 3,041804.
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In the central nervous system, synapses form thebasic functional units of connectivity betweentwo neurons. The formation, remodelling andelimination of synapses refine the micro circuitryin the brain. The synapse is a complex molecularmachine, which changes its structure andcomposition during neuronal development andplasticity. It contains hundreds of proteinschoreographed into a micron sized machineoverseeing the fidelity of brain function. Thecomponents of the synapses play a major role insynaptic transmission and synaptic plasticity,which are thought to underlie learning andmemory. Interestingly most of the diseases has adirect impact on the number, position andmovement of molecules in and out of synapsecontributing towards synaptic loss ordysfunction thus affecting the normal behaviourof the brain.
However, it has been an enigma how informationis processed at a single synapse by controllingfunction, position and regulation of severalmolecules.
This is partly because of the inaccessibility togarner information to resolve structures lessthan a few 100nm. The development of super-resolution imaging methods (Nobel Prize 2014)that break the diffraction limit allows monitoringthe real-time (milli-seconds) synapticorganization at the nanoscale (10-50nm). Thework in our lab attempts to dissect thefundamental role of dynamic nanoscaleorganization of synaptic molecules tounderstand how synapse process andrelay information. To achieve this we follow aninter disciplinary research paradigm at theinterface of high-end microscopy, molecularbiology and cellular neuroscience. All thisinformation is expected to contribute towards abetter understanding of how synapses functionat the molecular scale and provide fundamentalinsights into signal processing at singlesynapses in health and disease.
Molecular Organization At The Synapse
Schematic representation of the workflow for generating an objective classification of F-actin organization in dendritic spines
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Srikanth PadmalaAssistant Professor
T: +91 80 2293 3435
1. Meyer CT*, Padmala S* and PessoaL (2019) Dynamic threat processing.Journal of Cognitive Neuroscience.31(4):522-542.
2. Padmala S, Sirbu M and Pessoa L(2017) Potential reward reduces theadverse impact of negativedistractor stimuli. Social cognitiveand affective neuroscience.12:1402-1413.
3. Padmala S and Pessoa L (2011)Reward reduces conflict byenhancing attentional control andbiasing visual cortical processing.Journal of CognitiveNeuroscience. 23(11):3419-32.
4. Lim SL, Padmala S and Pessoa L(2009) Segregating the significantfrom the mundane on a moment-to-moment basis via direct andindirect amygdala contributions.Proceedings of the NationalAcademy of Sciences, USA. 106,16841-16846.
5. Padmala S and Pessoa L (2008)Affective learning enhances visualdetection and responses in primaryvisual cortex. Journal ofNeuroscience. 28(24):6202-6210.
I received a Bachelor’s degree in Biomedical Engineering from Osmania
University, Hyderabad followed by a Master’s degree in Biomedical
Engineering from the University of Memphis, USA. Then, I worked for
more than a decade in Dr. Luiz Pessoa’s laboratory of Cognition and
Emotion investigating brain mechanisms of emotional processing and
interactions between emotion, motivation, and cognition in healthy adult
humans using behavioural and functional MRI (fMRI) techniques. As a
National Science Foundation (NSF) Graduate Research Fellow, I
investigated interactions between appetitive and aversive processing
during perception and attention and received my PhD from the inter-
disciplinary Neuroscience and Cognitive Science (NACS) program at
University of Maryland, USA. After my PhD, I continued working at the
University of Maryland as an Assistant Research Scientist and joined
Centre for Neuroscience as an Assistant Professor in March 2019.
Selected Publications:
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Throughout our lives, emotional andmotivational factors influence our thoughts andactions. Hence, we need to understand howemotion, motivation, and cognition interact inthe human brain.
Knowledge of brain mechanismsunderlying these interactions is not only relevantto our healthy lives but also has potential clinicalrelevance. In mental disorders such as addiction,anxiety, and depression, cognitive impairmentsdue to compromised emotional and/ormotivational processing are extensivelyreported. Therefore, a deeper understanding ofbrain mechanisms underlying interactionsbetween emotion, motivation and cognition willhelp us better understand the anomalies inneurobiological mechanisms associated withthese disorders and potentially improvetreatment strategies.
Despite this, our understanding of howthese factors-interact in the brain is rudimentary.This is because the majority of the past workfocused on investigating emotional, motivationaland cognitive processing in an independentfashion
Our work attempts to fill some of thesecritical gaps in our knowledge base byinvestigating interactions between emotion,motivation, and cognition in the healthy adulthuman brain. We primarily employ behavioraland functional MRI (fMRI) methods combined
with psycho-physiological measurements (e.g.,skin conductance responses) in our research.
Additionally, we focus on understandinghow individual differences in self-reportedanxiety and reward-sensitivity influence theseinteractions.
Our most recent work is focused oninvestigating interactions between rewardmotivation and negative emotional processing.
During reward and no-reward conditionssignaled by an advanced cue, participants wereasked to ignore the central negative or neutraldistractor image and decide whether theperipheral bars were of the same or differentorientation. Potential reward reduced theadverse impact of negative distractors on taskperformance (Padmala et al., 2017).
Interactions Between Emotion, Motivation, And Cognition
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I graduated with a Ph.D. in molecular microbiology from the Institute of
Molecular and Cell Biology, National University of Singapore. I then joined
the laboratory of Prof. David Ginty as a post-doctoral research fellow in the
Department of Neuroscience, The Johns Hopkins University School of
Medicine in Baltimore, MD, USA. After completing my post-doctoral
training, I joined as an Assistant Professor of Neurobiology, Washington
University School of Medicine in St. Louis, MO, USA. In July 2013, I moved
my laboratory to the Centre for Neuroscience, Indian Institute of Science,
Bangalore.
Selected Publications:
Naren RamananAssociate Professor
T: +91 80 2293 3532
1. Chatterjee A, Chinappa K, RamananN and Mani S (2018) Centrosomeinheritance does not regulate cellfate in granule neuron progenitorsof the developing cerebellum.Cerebellum 17: 685.
2. Li CL, Sathyamurthy A, Oldenborg A,Tank D and Ramanan N (2014)Glycogen synthase kinase-dependent axon growth ismediated by SRF-dependenttranscription in CNS neurons.Journal of Neuroscience.34(11):4027-4042.
3. Lu PPY and Ramanan N (2012) Acritical cell-intrinsic role for serumresponse factor in glial specificationin the CNS. Journal ofNeuroscience. 32: 8012-23.
4. Lu PPY and Ramanan N (2011)Serum Response Factor is requiredfor cortical axon growth butis dispensable for neurogenesisand neocortical lamination. Journalof Neuroscience. 31:16651-64.
5. Donlea, JM Ramanan N andShaw, PJ (2009) Use-dependentplasticity in clock neurons regulatessleep need in Drosophila. Science.324: 105-108.
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The complexity of the mammalian centralnervous system (CNS) lies both in the number ofdifferent cell types generated duringdevelopment and in the intricate manner inwhich they interact to form functional circuits.We are interested in two broad questions:
(1) What are the molecular mechanisms regulatingaxonal growth during development and how thesemechanisms can be activated to promote axonalregeneration after injury.
My lab is interested in studying the cell intrinsicmechanisms that regulate axon growth duringdevelopment. Towards this end, we haveidentified a transcriptional pathway that is criticalfor developmental axon growth. Using molecularbiology and cell biology approaches, we arestudying the mechanisms by which genes in thispathway mediate axon growth. The knowledgegained from these experiments will be usedto study whether or how these mechanisms are
affected after nerve injury and whether thesemechanisms can be reactivated to promoteaxonal regeneration in the central nervoussystem.
(2) What are the mechanisms regulating neuralstem cells to astrological differentiation in thebrain? How do these mechanisms go awry ingliomas, the major tumours in the brain?
We have identified a novel pathway that is criticalfor astrocyte differentiation and maintenance inthe mouse brain. Studies are underway tounderstand the underlying mechanisms thatmediate astrocyte differentiation anddevelopment. It is our hope that the geneticpathways identified in our studies can enable usto understand better the biology of gliomas thathave their origin in astrocytes.
AXON GROWTH AND REGENERATION IN CNS
What are the cell-intrinsic mechanisms promoting axon growth during CNS development?
How can these mechanisms be reactivated to promote axonal regeneration followinginjury and disease?
ASTROCYTE DIFFERENTIATION DURING DEVELOPMENT AND IN DISEASE
What are the molecular mechanisms regulating neuralstem cell to astrocyte differentiation?
How do these mechanisms regulating astrocyte differentiation go awry causing gliomas – major tumours in the brain?
Neuronal And Glial Cell Development
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I received a B. Tech in Electrical Engineering from IIT Kanpur and a PhD in
Biomedical Engineering from the Johns Hopkins School of Medicine. For
the doctoral degree, I worked with Drs (Late) Kenneth Johnson, (Late)
Steven Hsiao, Ernst Niebur and Nathan Crone and studied the neural
mechanisms of high-gamma activity in both human and non-human
primates. My post-doctoral training was with Dr. John Maunsell in the
Department of Neurobiology at Harvard Medical School, where I studied
the neural mechanisms of gamma oscillations in non-human primates
Supratim RayAssociate Professor
T: +91 80 2293 3437
1. Dubey A and Ray S (2019) Corticalelectrocorticogram (ECoG) is a localsignal. Journal of Neuroscience. 39:4299-4311
2. Shirhatti V and Ray S (2018) Long-wavelength (reddish) hues induceunusually large gamma oscillationsin the primate primary visual cortex.Proceedings of the NationalAcademy of Sciences USA. 115:4489-94
3. Murty DVPS, Shirhatti V, RavishankarP and Ray S (2018) Large visualstimuli induce two distinct gammaoscillations in primate visual cortex.Journal of Neuroscience. 38: 2730-44.
4. Salelkar S, Somasekhar GM and RayS (2018) Distinct frequency bands inthe local field potential aredifferently tuned to stimulus driftrate. Journal of Neurophysiology.120: 681-692.
5. Subhash Chandran K S, Mishra A,Shirhatti V and Ray S (2016)Comparison of Matching Pursuitalgorithm with other signalprocessing techniques forcomputation of the time-frequencypower spectrum of brain signals.Journal of Neuroscience. 36: 3399-3408.
Selected Publications:
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Neural Mechanisms OfSelective Attention
Our senses convey rich and detailed informationabout the external world, but we can selectivelyattend to some details while ignoring others.This capacity for selective attention is critical forsurvival and essential for complex tasks.Problems with controlling and directingattention, such as attention deficit hyperactivitydisorder (ADHD), can impair the ability ofindividuals to function normally. Attentionalmechanisms have been studied at severaldifferent recording scales – from single neuronsin monkeys to diffuse population measures suchas electro or magneto encephalography(EEG/MEG) in humans. However, the relationshipbetween signals recorded from such differentscales is poorly understood.
The long-term goal of this research isto elucidate the mechanisms of attention bylinking the neural recordingsobtained from these vastly differentscales. In particular, we focus on particularoscillations in the brain, such as the alpha (~10Hz) or gamma rhythms (30-80 Hz), which are
modulated by the attentional load, and canreadily be recorded from both microand macroelectrodes. Several types of recordingscales are investigated.
In humans, we record using EEG electrodes andalso collaborate with neurosurgeons who workwith epileptic patients and record fromelectrodes placed directly on the brain (calledelectrocorticogram or ECoG). In non-humanprimates (NHPs) trained to perform anattention task, we record from microelectrodesas well as ECoG and EEG electrodes. Apart fromstudying attention, this approach allows us tounderstand the neural basis of EEG, which hasdirect applications in the diagnosis of braindisorders and in brain machine interfaces. Wealso develop signal-processing tools to studybrain signals, which are highly non-stationaryand often require special analysis techniques.
# Neurons
Monkey
Human
1 to afew ~ fewthousand ~Half amillion Millions
SpikesLocal field
Potential (LFP)
EEG
Electrocorticogram(ECoG)
Electrocorticogram(ECoG)
µ-ECoG
µ-ECoG
~100,000
STUDY OF ATTENTION AT MULTIPLE SCALES OF RECORDING
25
I obtained a Masters in Physics from Indian Institute of Technology
Chennai. My PhD training was with Prof. Eckart Gundelfinger (Dept. of
Neurochemistry & Molecular Biology) and Dr. Werner Zuschratter (Special
Lab for Electron and Laserscanning Microscopy) at Leibniz institute of
Neurobiology, Magdeburg, Germany. I did my postdoctoral training in the
Nano-photonics group of Prof. Brahim Lounis and Dr. Laurent Cognet at
the University of Bordeaux, France, and later in the Dynamics of Cell
growth and Cell Division group of Dr. Derek McCusker at the European
Institute Chemistry and Biology, University of Bordeaux, France. I joined
CNS as a Ramalingaswami fellow in September 2015, where I
study molecular mechanisms underlying neuronal polarity establishment.
Selected Publications:
Mini Jose DeepakRamalingaswami Faculty Fellow
T:+91 80 2293 2518
1. Nanguneri S, Pramod RT, EfimovaN, Das D, Jose M, Svitkina T, Nair D(2019) Characterization ofnanoscale organization of F-actininto morphologically distinctdendritic spines in vitro usingsupervised learning. eNeuro. 6(4).
2. Venkatachalapathy M., Belapurkar V,Jose M, Gautier A, Nair D (2019) Livecell super resolution imaging byradial fluctuations using fluorogenbinding tags. Nanoscale.11(8):3626-32.
3. Sartorel E, Unlu C, Jose M, Massoni-Laporte A, Meca J, Sibarita JB,McCusker D (2018)Phosphatidylserine and GTPaseactivation control Cdc42nanoclustering to counterdissipative diffusion. MolecularBiology of the Cell. 29(11):1299-1310.
4. Jose M. et al (2015) A quantitativeimaging-based screen reveals theexocyst as a network hubconnecting endocytosis andexocytosis. Molecular Biology of theCell. 26(13):2519-34.
5. Jose M. et al (2013) Robust polarityestablishment occurs via anendocytosis-basedcortical corrallingmechanism. The Journal of CellBiology. 200(4): 407-18.
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How do neurons differentiate?Differentiating mouse hippocampal neurons (Left-24 hrs and Right-4 days in vitro), colabelled with a combination of
antibodies against beta tubulin III (red) and Map2 (green). The neurons exhibit a symmetric to asymmetric growth along
development.
Neuronal Polarity And Development
Establishment of cell polarity plays a crucial rolefor development, motility and survival in alleukaryotic systems. Diffusion of bio molecules onthe plasma membrane creates asymmetry,generating cell polarity. Lipid homeostasis plays amajor role in creating this molecular asymmetry.My group focuses on addressing a fundamental,yet important question in neuroscience.
How is cell polarity established during neuronaldevelopment or how do the neuronsdifferentiate? Differentiation of neuronalprocesses into subtypes namely, axons anddendrites, remain to be a highly intriguing butcritical mechanism for survival during neuronaldevelopment. It plays a key role in establishingspecialized neuronal processes to form cell-cellcontacts or synapses, crucial for signal processingin the brain. Early in development, the shortneuronal processes called neurites grow similarto each other in a symmetric manner. A sharptransition during the growth period allows one ofthe processes to grow at a much faster ratecompared to the other processes, whichdevelops as the axon.
It has been found that there are molecular andstructural differences between axons and thedendrites. Interestingly, though differentapproaches have been adopted to intercept themolecular mechanism behind, a clear model onthis critical transition during development, whichdetermines neuronal survival, remains to beunderstood.
Lipid metabolism has been shown to hold thekey to major fundamental processes includingneuronal differentiation. In my project, I try tounravel the molecular mechanisms underlyingneuronal polarity using a multidisciplinaryapproach combining molecular biology, geneticengineering and single molecule basedsuperresolution microscopy. The role of lipidmetabolism in neuronal differentiation is studiedusing rodent hippocampal neurons as a modelsystem.
In summary, these studies would help us toidentify molecular mechanisms generating cellpolarity and allow us to understand how itcontributes to neuronal differentiation anddevelopment.
27
Selected Publications:
Sachin DeshmukhWellcome-DBT Intermediate Fellow
T: +91 80 2293 2830
I obtained my MSc in Biotechnology from MS University, Baroda
and my PhD in Neuroscience from the National Centre for Biological
Sciences (NCBS), Bangalore. I did post-doctoral work at the University of
California, Berkeley, University of Texas Health Sciences Centre at
Houston and Johns Hopkins University, Baltimore. My post-doctoral work
involved characterizing spatial and non spatial entorhinal cortex inputs to
the hippocampus by recording single neuron activity in awake, behaving
rats.
1. Wang C, Chen X, Lee H, DeshmukhSS, Yoganarasimha D, Savelli F,Knierim JJ (2018) Egocentric codingof external items in the lateralentorhinal cortex. Science 6417:945-949.
2. Saxena R, Barde W, Deshmukh SS(2018) Inexpensive, scalable camerasystem for tracking rats in largespaces. Journal of Neurophysiology.120: 2383–2395.
3. Deshmukh SS, Knierim, JJ (2013)Influence of local objects onhippocampal representations:landmark vectors and memory.Hippocampus. 23:253-267.
4. Deshmukh SS, Knierim JJ (2011)Representation of non-spatial andspatial information in the lateralentorhinal cortex. Frontiers inBehavioral Neuroscience. 5:69.
5. Deshmukh SS, Yoganarasimha D,Voicu H, Knierim JJ (2010) Thetamodulation in the medial and thelateral entorhinal cortices. Journalof Neurophysiology. 104:994-1006.
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How Does Hippocampus Create Representations Of Space?
We use In-vivo recordingof neuronal ensembleactivity from awake, freelymoving rats to study neuralcomputations in thehippocampal formation.
Neural Correlates Of Space & Memory In The Hippocampus
Space is the most conspicuous functionalcorrelate of rodent hippocampal neurons. Aprominent theory posits that hippocampal“place cells” constitute a spatial framework, andthat items and events of experience areorganized within this spatial framework to createa “cognitive map”. Cortical inputs to thehippocampus are channeled through the lateralentorhinal cortex (LEC) and the medialentorhinal cortex (MEC). While MEC encodespath-integration-derived spatial information, werecently showed that LEC encodes sensory-derived spatial as well as nonspatial information.Such sensory-derived information is critical tothe cognitive map, for anchoring the spatialrepresentation to the real world usinglandmarks, and for storing and processingnonspatial information in the context of spatialinformation.
Our primary research interest is to understandhow the hippocampal network creates acoherent representation of events within theirspatial context.
Unravelling the interplay of sensory-derivedspatial and nonspatial information brought in byLEC and the internally generated, path-integration-based spatial representation in MECis a crucial step in this endeavour.
We hypothesize that gating of sensoryinformation by LEC plays a role in the creationand maintenance of the representation of spacein the hippocampal system. Selecting relevantsensory information may be the vitalcontribution of LEC to cognitive map formationand function. We record activity of neurons inawake, behaving rats to test whether LEC gatessensory information for task relevance, andmeasure the effect of such gating on the activityof MEC and the hippocampus. Answers to thesefundamental questions will help decipher howthe cognitive map is created and used duringmemory formation.
29
I received my Bachelor of Science degree in Microbiology from Ramnarain
Ruia College, Mumbai University. I later joined Prof. Vidita Vaidya’s lab at
the Tata Institute of Fundamental Research, Mumbai, where I received
Master of Science degree in Biology. Here I worked on the effects of
norepinephrine receptors on neurogenesis, with a particular emphasis on
developing fast acting antidepressant drugs.
I received a PhD in Neuroscience at the Department of Medicine,
University of Fribourg, Switzerland. I worked on Notch signaling cascade in
neurodegenerative disorders for my thesis. During my PhD work, a
serendipitous discovery got me interested in studying astrocyte
physiology in mood disorders. After completing my PhD, I did a short
postdoc at EPFL, Switzerland studying astrocyte-neuron metabolic
coupling in depressive disorders. I joined Centre for Neuroscience in May
2017. Here we study the role of astrocytes in stress resilience and
depressive disorders.
1. Marathe S, et al (2017) Jagged1 IsAltered in Alzheimer's Disease andRegulates Spatial MemoryProcessing. Frontiers in CellularNeuroscience. 9;11:220.
2. Brai E, Marathe S, et al (2015)Notch1 Regulates HippocampalPlasticity Through Interaction withthe Reelin Pathway, GlutamatergicTransmission and CREB Signaling.Frontiers in Cellular Neuroscience.26;9:447.
3. Marathe S, et al (2015) Notchsignalinginto excitotoxicity induces neurodegeneration via erroneous cell cyclere-entry. Cell Death Differentiation.22(11):1775-84.
4. Marathe S, et al (2015) Notch inmemories: points to remember.Hippocampus 25(12):1481-8.
5. Yanpallewar S, Fernandes K,Marathe S, et al (2010) Alpha2-adrenoceptor blockade acceleratesthe neurogenic, neurotrophic, andbehavioral effects of chronicantidepressant treatment. Journalof Neuroscience. 30(3):1096-109.
Selected Publications:
Swananda MaratheINSPIRE Faculty Fellow
T:+91 80 2293 3621
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Although how neurons influence behavior hasbeen investigated in great detail, there has beenlittle clarity on the role played by astrocytes, afar more abundant cell type, in orchestratingbehavior. Astrocytes form an integral part ofthe synaptic machinery and a single astrocytecan contact and influence the function ofabout 100,000 synapses. They are extremelyimportant for normal synaptic function andmany brain disorders are associated withastrocytic dysfunction.
We are interested in studying how astrocytesand neurons communicate with each other tomodulate synaptic plasticity. We investigate therole of astrocytes in behavior with a particularemphasis on mood-related disorders such asanxiety and depression. We are currentlystudying Jagged-Notch signaling at astrocyte-neuron interfaces.
We have discovered that the mice lackingJagged1 in astrocytes have an anxiety anddepressive-like phenotype. Glutamate is able toinduce upregulation and extracellular secretion
of Jagged1 by the astrocytes, and the secretedJagged1 is able to activate neurons throughNotch1 receptors. Furthermore, Notch1receptors expressed in neurons interact withthe NR1 subunit of the NMDA receptors andthe loss of Notch1 expression in neurons resultsin reduced NMDA currents. We are exploringtheseJagged1-Notch1 mediated astrocyte-neuron interactions that are at the heart ofastrocyte-dependent pathophysiology ofanxiety and depressive disorders.
We are also investigating morphological andmolecular plasticity as well as novel mediatorsof astrocyte-neuron interactions relevant tostress resilience and depressive disorders.
Astrocyte-neuron Interactions In Mood Disorders
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EVENTS @ CNS
32
Open Days @ CNS
33
Pages From History
The Indian Institute of Science (IISc) wasfounded in 1909 as a result of the jointefforts of Jamsetji Nusserwanji Tata, theGovernment of India, and the Maharaja ofMysore. In 1886, Jamsetji Tata conceived of auniversity of science that will work for thebenefit of India, and in 1898 created anendowment for establishing such aninstitution. The Government of India thentook up the effort, and, in consultation withscientists in England and in India, decided tolocate the Institute in Bangalore, where theMaharaja of Mysore, Shri KrishnarajaWodeyar IV, donated 372 acres of land. TheInstitute was formally vested in 1909, thefoundation stone was laid in 1911, and thefirst batch of students started their studies inthe same year.Jamsetji Nusserwanji Tata
(1839 - 1904)H.H. Sri Krishnaraja Wodeyar IV
(1884 -1940)
Dear Swami Vivekananda,I trust, you remember me as a fellow traveler on your voyage from Japan to Chicago. I very
much recall at this moment your view on the growth of the ascetic spirit in India and the duty, not ofdestroying, but of diverting it into useful channels. I recall these ideas in connection with my scheme ofResearch Institute of Science for India, of which you have doubtless heard or read. It seems to me that nobetter use can be made of the ascetic spirit than the establishment of monasteries or residential halls formen dominated by this spirit, where they should live with ordinary decency and devote their lives to thecultivation of science, natural and humanistic. I am of the opinion that, if such a crusade in favor of anasceticism of this kind were undertaken by a competent leader, it would greatly help asceticism, science,and the good name of our common country; and I know not who would make a more fitting general ofsuch a campaign than Vivekananda. Do you think you would care to apply yourself to the mission ofgalvanizing into life our ancient traditions in this respect? Perhaps, you had better begin with a fierypamphlet rousing our people in this matter. I should cheerfully defray all the expenses of publication.
With kind regards,I am dear Swami
Yours faithfully,Jamsetji Tata
Historic Letter Of
J.N. Tata To Swami
Vivekananda
ON
23 November 1898
4
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Centre for NeuroscienceIndian Institute of Science, Bangalore -560012Karnataka, IndiaT: +91 80 22933431F: +91 80-23603323E: [email protected]
