GROUP B6MARGARITA BLAJEVACAITLIN H. CHEONGPARI CHOWDHARYWISSAM A. SAMAD

BROOKE THORNTON

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

Long-Term Potentiation

Long-lived ↑ in synaptic strength

LTP and memory

associativity

N – methyl – D – aspartate (NMDA) receptor

Pari

NMDA Receptor

Adapted from http://web.sfn.org/index.cfm?pagename=brainBriefings_schizophreniaAndCognition&print=on

NMDAR

Voltage – dependent glutamate receptor

Activated in LTP

Pari

AP5

D(-)-2-amino-5-phophonovaleric acid

NMDA –receptor antagonist

Intracerebroventricular (ICV) administration

Impairs water maze acquisition

Blocks LTP induction

Pari

Research Issue

What component of spatial learning do blocked NMDA receptors affect?

Can this effect be prevented?

Pari

Experimental Apparatus

Adapted from http://btc.bol.ucla.edu/mwm.htm

LEGEND

Quadrant 1

Quadrant 2

Quadrant 3

Quadrant 4

P

Pari

Hypothesis

Does an AP5-induced inhibition of NMDA receptor

functioning ALWAYS produce a learning deficit in

spatial learning?

Pari

PURPOSE:

TO DETERMINE HOW AP5 AFFECTS RAT PERFORMANCE IN A WATER MAZE TASK

Experiment 1

Brooke

Methodology

Habituation and training ‘upstairs’

½ AP5 rats and ½ aCSF rats

Trained in a water maze to find platform

Brooke

Escape latency decreases in aCSF rats over trials

FIGURE 1 a

Brooke

aCSF rats learnt and spent more time, over trials, in the quadrant with the

platform

FIGURE 1 b

Brooke

LTP is normal in aCSF rats

FIGURE 1 c

Brooke

Results

The rats implanted with AP5 had no decrease in escape latency

The rats with aCSF were able to learn the task

LTP is blocked only in AP5 rats

Brooke

Brooke

PURPOSE:

TO DISSOCIATE THE ALTERNATIVES OF SPATIAL LEARNING

Experiment 2

Margarita

Methodology

• pretrained in a different ‘downstairs’ water maze

• i.c.v. infusion of AP5 or aCSF

• trained on the ‘upstairs’ spatial task

Margarita

Hypothesis

If NMDA receptors are necessary for forming a spatial

representation of a new environment, an AP5-induced

deficit in learning should still be present

Margarita

aCSF and AP5 rats showed a decline in escape latency across trials

FIGURE 2 a

Margarita

FIGURE 2 b

Margarita

Both groups showed a strong bias towards searching in the training

quadrant

FIGURE 2 c

Margarita

FIGURE 2 d

Margarita

LTP Blockade in vivo

FIGURE 2 f

Margarita

PURPOSE:

TO SEE IF SPATIAL PRETRAINING REDUCES THE NECESSITY FOR HIPPOCAMPAL INVOLVEMENT IN SPATIAL LEARNING IN A NOVEL ENVIRONMENT

Experiment 3

Pari

Methodology

• Trained in the same spatial pretraining task downstairs

• Given either: ibotenic acid lesions to hippocampus

sham surgery left unoperated

• Trained on exactly the same spatial learning task upstairs

Pari

A lesion-induced deficit in escape latency and transfer test performance

was clearly apparent.

FIGURE 2 g

Pari

Implications

Spatial learning remains hippocampus-dependent

after previous training in a similar task

Pari

PURPOSE:

TO TEST WHETHER NON-SPATIAL PRETRAINING IS SUFFICIENT IN ELIMINATING THE AP5 DEFICIT IN LEARNING THE WATER MAZE

Experiment 4

Wissam

Methods

Extraneous cues were obscured

Platform was placed/hidden in a different location on each trial

Pre-trained downstairs, then AP5 and aCSF pumps put in, and trained in upstairs maze.

Wissam

FIGURE 3 a

Wissam

FIGURE 3 b

Wissam

FIGURE 3 c

Wissam

FIGURE 3 d

Wissam

Perforant Pathway

Adapted from http://thebrain.mcgill.ca/flash/a/a_07/a_07_cl/a_07_cl_tra/a_07_cl_tra.html

Wissam

FIGURE 3 e

Wissam

Results

Longer escape latencies “downstairs”

AP5 deficit in learning “upstairs” task reappeared.

aCSF group focused search around training quadrant.

AP5 group near-random searching in appropriate quadrant.

Wissam

Summary

Experiment

Significance

1NMDA receptors are essential for spatial learning.

2NMDA receptors are not necessary for spatial learning

3Proved spatial learning is hippocampal dependant.

4NMDA receptors are not necessary for non-spatial learning

Therefore, NMDAR are involved but not necessary for spatial and non-spatial learning .

Wissam

References

Bannerman, D. M., Good, M. A., Butcher, S. P., Ramsay, M., &

Morris, R. G. (1995). Distinct components of spatial learning

revealed by prior training and NMDA receptor blockade.

Nature , 378, 182-186.

Martinez, J. L., & Derrick, B. E. (1996). Long-term potentiation

and learning. Annual Review of Psychology , 47, 173-203.