Transcript Distinct Components of Spatial Learning Revealed by Prior Training

DISTINCT COMPONENTS OF
SPATIAL LEARNING REVEALED
BY PRIOR TRAINING AND NMDA
RECEPTOR BLOCKADE
Group B3
Abdullah, Barbara, Charles, Charmaine,
Margaret and Sarah
Sarah
OUTLINE
1.
2.
3.
4.
5.
Summary of the results
Confounding Variable: AP5 Administration
Controlling AP5 Administration
Supporting Evidence
Application to Human Studies
Barbara
SUMMARY OF FINDINGS
Exp.
1
Methods
- Male Lister rats given AP5 or
aCSF
- Trained in watermaze to find a
hidden escape platform
2
- Rats pre-trained in another
watermaze in separate lab
(downstairs)
- AP5 or aCSF infused
Results
-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
-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.
3
4
Methods
Results
-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 hippocampusdependent after previous training in a
similar task
- Must be that disrupting NMDA
receptors interferes with non-spatial
procedural learning
- 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 nearcomplete 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

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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 pretraining (& 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 nonspatial pre-training (when spatial learning is disrupting)
can account for normal performance in Morris Water
Maze
Barbara
CONTROLLING FOR DRUG DOSAGE :

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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)
Charmaine
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?
Sarah
APPLICATION TO HUMAN STUDIES

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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 NMDAdependent forms of LTP. Biochemical analysis showed
impaired NMDA function in mice.
Any Questions or Comments?