Lab 6 loss of function techniques slides(1)
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Transcript of Lab 6 loss of function techniques slides(1)
Questions You’ll Have Answered By The End of Lab…
• What’s wrong with just doing electrophysiology/functional imaging?
• How have psychedelic mushrooms contributed to our understanding of the brain?
• What in the world does Adam do when he’s not teaching?
The Problem with Electrophysiology/Functional Imaging
• Correlative• Still valuable information• Can point you in the right direction• Not the whole story
Xkcd.com
Outline
• Permanent Manipulations– Existing Lesions– Aspirated/Electrolytic Lesions– Ibotenic Acid– Focal Ischemia
• Reversible Manipulations– tDCS– TMS– Cortical Electrical Stimulation– Pharmacological Agents– Transient Cooling – Optogenetics
Existing Lesions
• Cortical Injury– Stroke– Head Trauma
• Confirm with Functional Imaging
• Phineas Gage– PFC
• Advantages and Disadvantages Boston.com and Science Photo Library
Aspiration/Electrolytic Lesions
• Aspiration– Literally remove with small
suction device– Surface Areas
• Electrolytic– Destroy with electrical
current– Areas at Depth
• Classic Technique• What vs. Where• Advantages and
Disadvantages
Padberg et al., 2010
Ibotenic Acid
• Derived from Amanita muscaria mushroom.
• Non-psychoactive component
• Neurotoxin– Excitotoxic Cell Death
• Destroys only cell bodies
• Advantages and Disadvantages Wikipedia.com
Focal Ischemic Infarct
• Cut off blood supply• Blood Vessel Ligation• Electrocoagulation• Similar to actual ischemic
events– Stroke– Compressed blood vessels– Sickle Cell Anemia– Etc.
• Advantages and Disadvantages
Nudo et al., 1996
Transcranial Direct Current Stimulation (tDCS)
• Apply continuous DC energy through skin/scalp into cortex
• Anode Cathode– Current Flow– Excitation/Inhibition
• Exceptions
• Mechanism of Action– Not completely understood
• Advantages and Disadvantages
George and Aston-Jones, 2010
Transcranial Magnetic Stimulation (TMS)
• Magnetic Induction– Apply coil– Pulse magnetic wave– Current induced– Single Pulse
• Depolarize
– rTMS
• Advantages and Disadvantages
George and Aston-Jones, 2010
Cortical Electrical Stimulation
• Lower Electrode into Brain• Low intensity, brief
current– Activation/priming
• Continuous Pulses– Deactivation– Constantly Refractory
• Deep Brain Stimulation• Advantages and
Disadvantagesnimh.nih.gov
Pharmacological Agents
• Muscimol– Amanita muscaria– Main psychoactive
compound– GABA agonist
• Systemic Administration
• Central Administration
• Advantages and Disadvantages Wikipedia.com
Transient Cooling
• Cool neural tissue to 20 degrees Celsius– Disrupt or abolish activity
• Brain desires homeostasis• Gyral and Sulcal
Implantation• Advantages and
Disadvantages• This is what Adam does all
day.Coomber et al, 2011
Optogenetics: The Future
• Microbially-derived Opsins– Control of ion channels
via light
• Light sensitivity– Bred in mice– Delivered in viral vector
• Advantages and Disadvantages
Web.mit.edu
Your Scenario
• You are a brand new association professor who has just started up their own lab.– Congratulations!
• You want to asses the function of your specific brain area of interest, but wish to go beyond electrophysiology/functional imaging.
• Your university has funds set aside for you to setup your lab, but has no one with whom you can collaborate to perform optogenetics (sad panda).
• Your job: Find a study which recorded from a brain area that you’re interested in and propose a loss of function experiment to test the hypotheses established by the study you read.
What Should be Included?• Length
– No more than 1 page, single spaced, AT THE MOST!• Summary of recording study
– Where did they record from/how did they record– What did they find– What was their model organism
• Methods– Loss of function method appropriate for your organism/question– Use the same stimuli/behavioral task as the recording study. If purely perceptual,
add a simple component that would assess perception of a stimulus (i.e. a button press or some such thing)
• Specific Predictions– Hypotheses based on electrophysiology/functional imaging
• Limitations and Potential Complications– How would you address these?
Details
• Due Date:– Monday, 3/2/15– BEGINNING OF CLASS (AKA 10:00 a.m. SHARP!)
• Even 1 minute late will incur a penalty
– Email or Hard Copy• All technology-related excuses will be thoroughly scrutinized
for bovine excrement.– If you don’t get an confirmation email from me, I didn’t receive it!
• 1 page, at the most!– Could easily complete this assignment in less if all
elements are included