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The morphological basis of synaptic plasticity and learning in the mammalian CNS

ReferenceS08513
Principal Investigator / Supervisor Professor Mike Stewart
Co-Investigators /
Co-Supervisors
Institution Open University
DepartmentLife, Health & Chemical Sciences
Funding typeResearch
Value (£) 216,277
StatusCompleted
TypeResearch Grant
Start date 01/01/1998
End date 16/08/2001
Duration43 months

Abstract

Elucidation of mechanisms that underlie the formation and loss of memory, is a major challenge in neurobiology. A key to understanding these mechanisms is believed to lie with investigation of induceable changes in neural circuitry at the level of synapses. The cellular machinery of use-dependent synaptic modifications has been extensively studied via the paradigm of hippocampal long-term potentiation (LTP). However, relating LTP per se to a memory-associated synaptic change remains a difficult issue. One feasible way to approach this is to combine induction of LTP with a hippocampus-dependent learning task in one animal. Therefore the objectives of the proposed work are: in the hippocampal dentate gyrus of the rat, 1) to build on our earlier research and further elucidate changes in synaptic structures associated with different phases of LTP, and of spatial learning using newly developed methods of quantitative optical and electron microscopy including stereology; 2) to establish time-dependent changes in the expression and patterns of Neural Cell AdhesionMolecule (NCAM) epitopes labelled with immunogold at the level of synapses, following induction of LTP, and spatial learning; 3) to determine whether the changes associated with LTP, and those associated with spatial learning, are occluded when both potentiation, and learning are performed in the same animal. 4) to evaluate the potential impact of observed synaptic changes on synaptic transmission using computer simulation experiments with: a) a realistic compartmental neuron, b) diffusion of neurotransmitter in extracellular space, and c) fast calcium influx into presynaptic terminals.

Summary

unavailable
Committee Closed Committee - Animal Sciences (AS)
Research TopicsX – not assigned to a current Research Topic
Research PriorityX – Research Priority information not available
Research Initiative X - not in an Initiative
Funding SchemeX – not Funded via a specific Funding Scheme
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