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Role of Endocannabinoids, or New Memory Implant?

presentation for Cognition & the Brain
by

Chris Newhard

on 6 December 2011

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Transcript of Role of Endocannabinoids, or New Memory Implant?

Results of Primary Source Memory Implants Give Rats
Sharper Recollection Memory encoding in hippocampal ensembles is negatively influenced by cannabinoid CB1 receptors Discussion Role of Endocannabinoids,
or New Memory Implants? New brain implant:
-restores lost memory function
-enhances recall of new info Crucial step in developing neuroprosthetics:
-would help with dementia, stroke, other brain injuries
-however, far from human implementation Hampson, Robert E.a; Sweatt, Andrew J.a; Goonawardena,
Anushka V.a; Song, Dongb; Chan, Rosa H.M.b; Marmarelis,
Vasilis Z.b; Berger, Theodore W.b; Deadwyler, Sam A.a Behavioural Pharmacology:August 2011 - Volume 22 -
Issue 4 - p 335–346doi: 10.1097/FBP.0b013e3283473bfd Basic Idea: Give drugs to rats, see the effects on memory Delay NonMatch to Sample: [DNMS memory task] 1) Sample Response (SR) - two levers, one is extended; rat sees and touches the extended lever 2) Delay Phase - rat is distracted for up to 30 seconds 3) NonMatch Phase - both levers are presented, rat has to touch the opposite lever to get reward CB1 (cannabinoid receptor) endocannabinoids -endogenous
-bind to CB1
-decrease DNMS performance URB597 & URB602 -artificial
-inhibit enzymes that digest
endocannabinoids
-decrease DNMS performance WIN 55212-2 -artificial
-potent agonist to CB1
-decreases DNMS performance Rimonabant -artificial
-antagonist to CB1
-opposite of WIN
-increases DNMS performance CA1 -role in acquiring new memories
-emits event specific firing patterns Neural firing patterns
can be recorded
from ensembles Recorded patterns
can be played back
to same neurons Procedure: Rats are trained at the DNMS memory task
Surgery: drug delivery minipump installed, neuron recording apparatus installed
Relearn the DNMS memory task to same standard
Treatment with drugs for two weeks (simulating long term drug use in humans)
Variable condition testing of DNMS occurs
CA1 firing patterns are recorded for rats treated with rimonabant, during SR
Playback of firing patterns to CA1 for rats treated with WIN (see if effect is same as rimonabant)
URB's are adminstered as a control to confirm endocannabinoid binding effect Benedict Carey
June 17, 2011
New York Times Experiment confirmed results of earlier studies were also true for chronic exposure WIN suppresses hippocampal encoding in DNMS task
Rimonabant enhances coding DNMS Performance after chronic infusion WIN effect is delay-dependent: performance was greatly suppressed only at longer delays
Rimonabant improves performance only at longer delays Relative Neuron Firing Rates (figure 2d)
Rimonabant greatly increased the number of neurons firing during SR
WIN only slightly decreased the number of neurons firing during SR
Therefore, the strength of the neural signaling during SR correlates with increased performance for longer delay periods.

Results were due to cannabinoids:
URB597 and URB602 had effects similar to those of WIN.
Like with WIN, the effects could be reversed by infusion with rimonabant.
URB compounds act specifically to increase the levels of endocannabinoids
This confirms that the endocannabinoids affect the DNMS performance and hippocampal encoding.
CA1 electrical stimulation mimicking neural patterns improved performance after WIN had been administered.
The performance increased almost back to level of the nondrug control
Conclusions of Primary Source: -Long term treatment of CB1 agonists chronically depresses performance on DNMS
Effect can be alleviated by antagonist
-Changes in hippocampal neuron recordings correlate with changes in DNMS performance
-Recorded neural firing patterns can be replayed as electrical stimulation
Mimics effect of antagonist
-Endocannabinoids play a major role in the encoding of hippocampal memory in event specific contexts
Does the NY Times article
accurately convey the findings
of the its source? Does this article accurately convey the findings of the journal article? Yes and no.
It only talks about the interesting part: artificial memory stimulation
It fails to mention in detail the extensive work confirming the role of endocannabinoids in the hippocampus
It falsely asserts that the electrical stimulation implant was the focus of the research
Questionable Quotes: “To test the effect of the implant, the researchers used a drug to shut down the activity of CA1.”
The experiment used stimulation (the implant) to test the effect of the drug, not the other way around
“The implant acted as if it were CA1, at least for this one task.”
The rat’s memory would not be able to function without CA1. The implant only enabled CA1 to function properly, it did not replace it.
Comparing the Titles: Memory encoding in hippocampal ensembles is negatively influenced by cannabinoid CB1 receptors
Memory Implant Gives Rats Sharper Recollection
New York Times Article Primary Literature Source new brain implant!
restores lost memory
strengthens recall
precursor to making
neuroprosthetics
could solve dementia
and other ailments
could keep elderly out
of nursing homes
cannabinoids chronically affect
the brain with long term drug use
CB1 activity directly affects
hippocampus function
electrical stimulation reverses
detrimental effects of WIN
Therefore, endocannabinoids
play a major role in the encoding
of hippocampal memory
Jessica Ziegler
Chris Newhard Cognition & the Brain
December 6, 2011
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