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Title: The role of metabotropic glutamate and NMDA receptors in hippocampal long-term potentiation and spatial learning
Author: Martin, S. J.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1999
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The aim of the present thesis was firstly to investigate whether the behavioural deficit resulting from NMDA receptor blockade reflects a genuine learning impairment, rather than a disturbance of some other aspect of brain functioning. The behavioural test used was a reference memory task in the watermaze, the learning of which is highly sensitive to hippocampal dysfunction. It has been claimed that he apparent learning deficits caused by the application of NMDA receptor antagonists may be secondary to sensorimotor disturbances, or drug-induced brain damage. Behavioural and histological analysis in the present study was not consistent with either of these two possibilities. However, owing to the fact that NMDA receptor blockade does indeed cause a number of side effects, subsequent experiments investigated the role of a novel class of receptor, the metabotropic glutamate receptor (mGluR), in both LTP and spatial learning. Previous studies have suggested that mGluR activation is necessary for both LTP induction and the acquisition of spatial memories. However, in the studies described herein, a broad-spectrum mGluR antagonist, MCPG, caused a modest impairment in spatial learning, but only under certain circumstances. Moreover, MCPG had no effect on the induction of LTP in vivo, despite the fact that the application of MCPG successfully blocked the increase in spontaneous hippocampal activity induced by the application of an mGluR agonist, ACPD. The role of mGluRs in hippocampal functioning is discussed in the light of these findings. Finally, electrophysiological experiments were conducted in order to investigate the activity-dependent reversal of LTP. It was found that the delivery of low frequency stimulation within 2 min of LTP induction caused a total reversal of LTP, but had little effect on baseline EPSPs when delivered alone. The ability to selectively erase recently induced potentiation in this way might provide an alternative to pharmacological intervention in future studies of the role of LTP-like mechanisms in memory storage.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available