How do we infer a relationship between brain and behavior?
- induce gain of function
(issue, brains are delicate and interconnected. Nothing is acting in isolation)
Ceiling effect? Upsetting balance of networks that can actually lead to impairment.
-induce a loss of function. (fusiform gyrus damage: prosopagnosia)
- moniter behavior and brain activity simultaneously
(FMRI has many limitations, like hippocampus working really hard all the time.
Sometimes can’t do a true experiment!
What do scientists mean by “no one ideal method”
No one time/spatial scale. Systems level understanding and small levels for invidual roles.
Tradeoff between spatial and temporal resolution.
How do you understand the thoughts of a rat?
Operant Conditioning, ask them to make choices.
- morris water maze
- 5 choice serial reaction time task (visuospatial attention), measure of MOTOR IMPULSIVITY (when they go too soon they get a shock))
- conditioning
- tmaze (do you want more reward for x cost?)
QUALITY OF MODEL IS DETERMINED BY QUALITY OF ASSAY
- forced swim test measures depression HOWEVER it can also show that animals learn to give up early with repeated trials. not the best.
Why do we use animal models?
THey actually model us! Very similar to us, animal cognition is sophisticated!!
What makes us different is our
- syntax
- throw overhand
- run long distances
Rats have our equivalent of a pfc, they have a medial temporal cortex.
What are the different ways to administer a drug?
Intramuscular (IM): acts quickly, but degrades muscle and isn’t reccomended.
Intravenous (IV): great, tail vein popular (but does cause some stress!!!- better for blood draw)
Subcutaneous (SC): needle under the skin, but doesn’t hit blood, so takes longer and more metabolism, meaning its less potent.
Intraperitoneal (IP): most common, where your guys are, easy, not stressful. rats like some drugs and not others.
Intraventricular: direct to ventricles of the brain. Gets you around BBB but very invasive.
Drug studies use multiple doses (often to see an inverted U shape. Dose response curve.
- Within subjects design (control and conditions inside same animal) not invasive or unpleasant.
What is Stereotaxic Surgery?
Bars and Measurements to get precise measurements. Use BREGMA as a landmark in at atlas to get exact lesions.
Animals have to die after to ensure you hit the right spot tho :(
What are various lesion methods? Issues with these?
- Chemical lesions (excitotoxic)
- quinolinic acid
- ibotenic acid
Spread more or less depending on the chemical. Destroy a specific area. - Destory a specific systems not killing whole areas
6-OHDA, kills dopamine but not other neurons.
57DHT: serotonin depletion - Reversible Lesions (inactivations)
- insert cannula, and on testing day, inject fluid (baclofen (GABA B) and Muscimol (GABA A) agnoists.
Strong inhibition of a brain region.
Within subjects desing. Shows you what happens when those areas are there/when they’re not!
ISSUES?
- Testing window: rats recover quickly
- Testing too quickly, rats may still be in recovery
- Bilateral usually, but unilateral happens too, CONTRALATERAL DISCONNECTION can show you if the regions are talking to each other. Impair one on each side.
What are invasive electrical recording methods?
- INtracellular unit recording. Very hard to puncture.
- extracelluar unit: more common, APs look inverted
- multiple unit: drop a grid
- invasive EEG: directly on the brain
What is single cell recording?
Looking at cell firing patterns and populating coding.
Rats presented with different environments, stimlui and behaviors it can perform. Drop tetrodes in Medial pFC (rats don’t have a dorsolateral pfc) **which one do rats not have??
- recording lots of neurons, and see whih respond to what? Combo of neurons releavl itself. Infer from population activity!!
Alternatively:grandmother cell that fires for one thing “sparce coding” (doesn’t really make sense?)
What is convergence/Divergence?
Paralell processing, distriubted representations. Allowing for population coding.
What is the halle berry neuron?
Neuron that fires only for Halle Berry. Drawings of her, her written name!!
Found this by looking at pt.s with epilepsy.
(near medial temporal lobe)
Firing for the concept of halle. CONCEPT CELLS?
NOT just a visual representation.
Doesn’t fire for other things. Population coding is the norm, but the brain does have this sparse coding too.
Other ones: Batman, Sidney opera house (even if you think it is), Jennifer anniston (not brad pitt)
SOme high converge and some population coding!
What are optogenetics?
light sensitive ion channels
G couples protein receptors.
(channelrhodopsin, and halorhodopsin)
Requires transgenics into chromosomes, expressed in only dopamine areas or in PFC, specific systems targetted!!! NO lesions or chemical stuff.
Hard to get started tho!!
