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Distinct Components of Spatial Learning Revealed by Prior Training and NMDA Receptor Blockade D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil | Carol Rego

D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

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Page 1: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

Distinct Components of Spatial Learning Revealed by Prior

Training and NMDA Receptor Blockade

D.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

Page 2: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

Overall Evaluations

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

Alternate Interpretation of the Results

Further Exploration

Table of Contents

Carol Rego

Page 3: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

Overall Evaluations

Carol Rego

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

exploration during the course of the study.

Page 4: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

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

Overall Evaluations

Carol Rego

Page 5: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

Overall Evaluations

Carol Rego

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

expression.

Page 6: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

Study focused on hippocampus

Actually three different pathways

Unexplored Pathway of LTP

Herman Gill

Page 7: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

Unexplored Pathway of LTP

Herman Gill

Pathway Input

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

Mossy Fibre Pathway Dentate Gyrus (DG)

Schaffer Collateral Pathway Cornu Ammonis III (CA3)

Page 8: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

Unexplored Pathway of LTP

Herman Gill

Perforant

Mossy Fibre

Schaffer Collateral

Page 9: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

Unexplored Pathway of LTP

Herman Gill

Perforant

Mossy Fibre

Schaffer Collateral

LTP is NMDA-independent in mossy fibre pathway

Page 10: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

In CA1 and DG◦ NMDA responsible

for LTM retrieval

In CA3◦ NMDA responsible

for spatial recognition

Unexplored Pathway of LTP

Herman Gill

LTM Retrieval

Spatial

Recognition

Page 11: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

Difference in performance with regards to age

Declines continuously beginning at earliest age

Age Anomalies

Bonnie Chan

Page 12: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

Gender Anomalies

Bonnie Chan

Gender Cues Efficiency

Male Geometric Fast

Female Landmark/Multiple Slow

Page 13: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

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

Page 14: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

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

Alternate Interpretation

Anastasia Christopher

Page 15: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

Stressful situations◦ Stress can impair performance on specific

activities

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

Alternate Interpretation

Anastasia Christopher

Page 16: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

Findings:

◦ Stress can cause amnesic symptoms in working memory

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

Alternate Interpretation

Anastasia Christopher

Page 17: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

Alternate Interpretation

Anastasia Christopher

Page 18: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

Connection:

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

Alternate Interpretation

Anastasia Christopher

Page 19: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

Further Studies

Sarah 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

Page 20: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

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

Page 21: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | 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

Conclusion

Carol Rego

Page 22: D.M. Bannerman, M.A. Good, S.P. Butcher, M. Ramsay & R.G.M. Morris GROUP A3 Bonnie Chan | Anastasia Christopher | Herman Gill Marisa Leung | Sarah McNeil

This concludes our presentation

We will be happy to address any questions you may have