This document discusses various techniques for assessing brain function beyond electrophysiology and functional imaging alone. It describes methods for both reversible and permanent manipulations of neural tissue, including transcranial direct current stimulation, transcranial magnetic stimulation, cortical electrical stimulation, pharmacological agents, transient cooling, optogenetics, as well as existing lesions, electrolytic lesions, ibotenic acid lesions, and focal ischemia. The document emphasizes that while electrophysiology and functional imaging can provide correlational information and point researchers in the right direction, loss of function techniques are also needed to fully understand brain function. It notes that both reversible and irreversible methods each have advantages and disadvantages.
1. Loss of Function Techniques
Or
“Why electrophysiology needs a
buddy.”
2. 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?
7. Existing Lesions
• Cortical Injury
– Stroke
– Head Trauma
• Confirm with Functional
Imaging
• Phineas Gage
– PFC
• Advantages and
Disadvantages Boston.com and Science Photo Library
8. 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
9. Ibotenic Acid
• Derived from Amanita
muscaria mushroom.
• Non-psychoactive
component
• Neurotoxin
– Excitotoxic Cell Death
• Destroys only cell
bodies
• Advantages and
Disadvantages Wikipedia.com
10. 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
14. 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
15. 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
20. 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
25. 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
26. 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.
27. 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?
28. 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
29. OMG!!! A RESEARCH ASSIGNMENT!?!?
WHERE DO I BEGIN???
• Web of Science
– Meet your new best friend
• Lib.ucdavis.edu
– Electronic Databases A-Z
• Go to “W”
• Select “Web of Science” vpn
• Demo to follow
• You may ask me any questions and I will be totally
willing to help both in lab today and via email.
