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Title: The role of the NMDA receptor in the hippocampus in certain forms of learning
Author: Davis, Sabrina
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1991
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The aim of this thesis is to test more rigorously the hypothesis that suggests that hippocampal NMDA receptors are involved in that type of learning attributed to the hippocampus through the induction of LTP and to test its effect on reference and working memory. In the first experiment a range of concentrations (5mM, 13mM, 20mM, 30mM, 40mM) of D-2-Amino-Phosphonopentanoate (D-AP5) were chronically infused (icv) into rats, at a rate of 0.5μl a day for 14 days. Control animals consisted of either sham and unoperated rats, or rats infused with aCSF. During the 14 day experimental period rats were tested on a spatial reference task in the open field water maze for 6 days and then an attempt to evoke LTP in each rat was made. At the end of the experiment micro dialysed samples of extra cellular fluid were taken from the left hippocampus for 2 hours. Finally, tissue samples from 5 brain areas, including the right and left hippocampus were dissected out and the exact content of AP5 in the brain during the experimental period was measured using high performance liquid chromatography (HPLC). The animals were regrouped according to the whole tissue concentration of AP5 in the hippocampus. The results showed a dose dependent impairment of spatial reference memory that correlated with the dose dependent blockade of the induction of LTP. The amount of AP5 recovered from the extracellular fluid of the hippocampus was estimated to be compatible with binding studies showing percentage receptor occupancy and electrophysiological studies showing the amount of AP5 required to block LTP in the hippocampal slice. In the second experiment a single concentration known to impair spatial reference memory and block the induction of LTP (30mM D-AP5) was used to test animals' ability to learn a spatial working memory task in the open field water maze. AP5 caused no impairment in working memory when the delay between trials was short (30s). When the delay was extended to 2 hours or 5 hours however, animals infused with AP5 showed a significant impairment. Also at the 5 hour delay, control animals began to show a trend towards showing a slight impairment in the task. The results from this thesis suggest that the activation of the NMDA receptor is necessary for the processing of more permanent or long term information required in a spatial task but is not necessary for information required for only brief periods of time. The hypothesis that the physiological activity underlying learning is a form of plasticity similar to that seen with LTP is strengthened with empirical evidence that shows a correlated dose dependent impairment of spatial reference memory and blockade of LTP.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available