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Title: Short and long term plasticity in mice lacking fyn tyrosine kinase and associated N-methyl-D-aspartate receptor signalling molecules
Author: Roylance, Alistair James
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1999
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The N-methyl-D-aspartate (NMDA) type of glutamate receptor has important functions in the processes of neuronal development, forms of neurodegeneration, epilepsy, pain and especially in synaptic plasticity and forms of learning and memory. An NMDA receptor dependent form of synaptic plasticity, long-term potentiation (LTP), has been proposed as a cellular correlate of memory. The cellular and molecular mechanisms that underlie this form of synaptic plasticity are at the present time unclear. The NMDA receptor is part of a macromolecular complex that mediates both the localisation of the receptor and its interactions with signalling molecules that activate the intracellular pathways responsible for the long lasting changes in synaptic efficacy. This thesis details results of experiments investigating long and short-term plasticity in mice lacking signalling molecules associated with NMDA receptor. The in vitro hippocampal slice preparation and extracellular and intracellular electrophysiological recording techniques were used to investigate plasticity in mice lacking the non-receptor tyrosine kinase fyn, focal adhesion kinase (FAK) and the ras guanine nucleotide releasing factor (ras-GRF). Ras-GRF knockout mice displayed normal NMDA receptor dependent LTP in area CA1 of the hippocampus and have been reported to show normal spatial learning in the Morris water maze (which is dependent on hippocampal function). Mice with disrupted FAK function also showed normal LTP in area CA1 of the hippocampus. Fyn tyrosine kinase deficient animals have been reported to show several neurological phenotypes, including impaired LTP induction in area CA1 of the hippocampus. This effect was found to be dependent upon the genetic background of the animal and independent of disruptions to hippocampal morphology. Short-term plasticity (paired pulse facilitation) was reduced in mice lacking fyn tyrosine kinase, an effect which was shown to be independent of age and genetic background. The mechanisms by which fyn mediates these changes were investigated through the use of experiments modulating the probability of neurotransmitter release.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available