Distinct Components of Spatial Learning Revealed by Prior Training and NMDA Receptor Blockade

Distinct Components of Spatial Learning Revealed by Prior Training

and NMDA Receptor BlockadeD.M. Bannerman, M.A. Good, S.P. Butcher,

M. Ramsay & R.G.M. Morris

GROUP A3Bonnie Chan | Anastasia Christopher | Herman Gill

Marisa Leung | Sarah McNeil | Carol Rego

Overall Evaluations

Methodological Critiques◦ Unexplored Pathway of LTP◦ Age and Gender Anomalies ◦ Pharmacological Side Effects

Alternate Interpretation of the Results

Further Exploration

Table of ContentsCarol Rego

Overall EvaluationsCarol Rego

The purpose of the study was very non specific, which allowed for further

exploration during the course of the study.

Experiment Evaluation

Experiment 1 • injection of AP5 caused learning deficit Experiment 2

• found contradicting results where the AP5 rats learned quite well despite complete LTP blockade

Experiment 3 • NMDA receptors are not necessary for all hippocampus dependant spatial learning

Experiment 4 • AP5 rats, given non-spatial pretraining, a learning deficit was observed



NMDA receptors are not necessary for all hippocampus dependant spatial learning, but NMDA receptor dependant plasticity is dependent on the hippocampus for its

expression.

Study focused on hippocampus

Actually three different pathways

Unexplored Pathway of LTPHerman Gill


Pathway Input

Perforant Pathway Entorhinal Cortex II, III (EC2 & EC3)

Mossy Fibre Pathway Dentate Gyrus (DG)Schaffer Collateral Pathway Cornu Ammonis III (CA3)


PerforantMossy FibreSchaffer Collateral


PerforantMossy FibreSchaffer Collateral

LTP is NMDA-independent in mossy fibre pathway

In CA1 and DG◦ NMDA responsible

for LTM retrieval

In CA3◦ NMDA responsible

for spatial recognition


LTM RetrievalSpatial Recognition

Difference in performance with regards to age

Declines continuously beginning at earliest age

Age Anomalies Bonnie Chan

Gender Anomalies Bonnie Chan

Gender Cues Efficiency Male Geometric FastFemale Landmark/Multiple Slow

Common critique/concern

Effects of the drugs used to block NMDA receptors not well researched

Side effects may cause a decrease in performance◦ (i.e.) due to drowsiness, disorientation

Solution Gene knockout?

Pharmacological Side Effects

Bonnie Chan

Stress Impairs Performance in Spatial Water Maze Learning Tasks (1999)◦ By Christian Holscher

Alternate InterpretationAnastasia Christopher

Stressful situations◦ Stress can impair performance on specific

activities

How altered fear conditions and stress perception can account for the impaired spatial learning


Findings:

◦ Stress can cause amnesic symptoms in working memory

◦ Non-handled rats were slower in a spatial learning task


Connection:

◦ Alternative interpretations for this research paper Experiment 2 no deficit; handling Experiment 3 stress was not an issue Experiment 4 extramaze cues


Further StudiesSarah McNeil

Evidence Supporting Evidence Against

Same results found in gene knockout studies

In nature, large scale EPSP’s do not occur during information processing

Training in the brain uses same pathways as LTP and causes same synaptic efficiency

Drug and gene knockout can have other side effects that skew data

LTP can occur in other regions of the brain (i.e. amygdala)

Unethical to test LTP in humans and cannot extrapolate data across species

There is lots of evidence to suggest that LTP might be similar to the neural mechanism

that the brain uses in learning and memory but the conclusion can not be made that the

mechanisms are the same.

Further Studies – Conclusion

Sarah McNeil

Provided subsequent analyses of their hypothesis creating a concrete conclusion

However:Left several possible causal pathways unexplored

Failed to account for pharmacological side effects, age, and gender of subjects

Possible misinterpretation of results

Further studies have shown some validity in Bannerman et al results

ConclusionCarol Rego

This concludes our presentation

We will be happy to address any questions you may have

Distinct Components of Spatial Learning Revealed by Prior Training and NMDA Receptor Blockade

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