DISTINCT COMPONENTS OF SPATIAL LEARNING
REVEALED BY PRIOR TRAINING AND NMDA RECEPTOR BLOCKADE
Group B3Abdullah, Barbara, Charles, Charmaine,
Margaret and Sarah
OUTLINE
1. Summary of the results 2. Confounding Variable: AP5
Administration 3. Controlling AP5 Administration4. Supporting Evidence 5. Application to Human Studies
Sarah
SUMMARY OF FINDINGS Exp. Methods Results
1
- Male Lister rats given AP5 or aCSF - Trained in watermaze to find a hidden escape platform
-Rats given AP5 failed to learn: no decrease in escape latency but failed to search within the appropriate quadrant of the pool - AP5 also blocked rat’s capacity for LTP - Rats infused with sCSF learned task normally
2
- Rats pre-trained in another watermaze in separate lab (downstairs) - AP5 or aCSF infused
-Rats treated with AP5 learned well: showed steady decrease in escape latency- AP5 rats were slower than aCSF group- Still showed blockage of LTP- Spatial pre-training in a different location improved AP5 deficit seen in experiment 1 (despite block of LTP)
Barbara
SUMMARY OF FINDINGS Exp
.Methods Results
3
-Rats were trained in downstairs spatial pre-training task-then given: ibotenic acid lesions, sham surgery, or left un-operated on - Then, trained on exactly the same spatial learning task upstairs
- Lesion induced deficit was evident - Spatial learning is hippocampus-dependent after previous training in a similar task - Must be that disrupting NMDA receptors interferes with non-spatial procedural learning
4
- Rats pre-trained in environment that minimized the opportunity for spatial learning - Curtains were drawn around maze, platform hidden in different location every trial
- AP5 deficit in learning task upstairs reappeared - AP5 groups also showed near-complete blockage of LTP - Non-spatial pre-training fails to prevent the AP5 deficit of spatial learning
Barbara
OVERALL CONCLUSIONS
Results show significant triple interaction between drug group, pre-training and testing With NO pre-training, rats treated with AP5
cannot learn Non-spatial pre-training allowed some level of
learning Spatial pre-training mostly lifter AP5 induced
deficits
AP5 infusion leading to blockade of LTP disrupts both spatial and non-spatial components of water maze task
Barbara
AMOUNT OF AP5 ADMINISTRATION Experiment 4: Test effects of non-spatial pre-training
Results demonstrate that AP5 in non-spatial pre-training (& LTP blockage)= poor performance in maze reappeared
HOWEVER, amount of AP5 administered was not strictly controlled for
Consequence of lack of control: excess administration of AP5 would disrupt NOT ONLY spatial, but non-spatial components of Water Maze learning
Need another experiment to control for amount of AP5 administered!
Why control for this? Can directly measure if non-spatial pre-training (when spatial learning is disrupting) can account for normal performance in Morris Water Maze
Barbara
CONTROLLING FOR DRUG DOSAGE : Study: Testing the NMDA, LTP and Cholinergic Hypothesis of Spatial
Learning
Experiment: Pre-trained in non-spatial task Then injected with NMDA and Muscarninc Retested in Morris Water Maze
Findings: These antagonists did NOT affect rat’s ability to
apply instinctive behaviours (i.e. using the platform as refuge) in an adaptive manner
Plastic changes involved in a acquiring task occur in sensory, motor and other cortices (not places specifically implicated in spatial learning)
Barbara
SUPPORTING EVIDENCE
Aim/Methods:
To evaluate the ability of the conventional NMDA antagonist CGS19755 (CGS) to block LTP induced by long (125 ms) trains of high-intensity pulses, and the ability of non-spatially pre-trained rats to acquire the maze task when given the same dose of CGS.
Expt. 2 explored the role of NMDA receptors in visual discrimination learning relevant to the water maze task.
The role of NMDA receptors and NMDA-mediated hippocampal (LTP) in spatial learning was studied in rats using the competitive, systemically administered NMDA receptor antagonists CGS19755 and NPC17742
Charmaine
CONCLUSIONS
Rats given non-spatial pre-training in the general strategies required in the task, acquired it as
effectively as controls when trained under a dose of CGS that completely blocked LTP in the
dentate gyrus of the same rats
Charmaine
Charmaine
Question:
It is not known why hippocampal damage impaired
performance of the water maze task even though the rats were capable of acquiring spatial information or learning a place response?
Charmaine
APPLICATION TO HUMAN STUDIES
Experiment: Attempted to determine whether neocortical LTP
was deficient in Alzheimer’s Disease (AD) patients as well as in APP/PS1 mice – an AD animal model.
Then examined LTP deficit in relation to NMDA receptor abnormalities.
Compared AD patients with matched controls on a paired associative stimulation task
Analyzed neocortical and hippocampal brain slices of APP/PS1 mice
Results: AD patients and mice both showed a deficit in
NMDA-dependent forms of LTP. Biochemical analysis showed impaired NMDA function in mice.
Sarah
Any Questions or Comments?
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