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Dentritic and synaptic targeting of mRNAs for the AMPA-type glutamate receptor subunits in hippocampal pyramidal cells.

ReferenceBB/C502773/2
Principal Investigator / Supervisor Dr Claudia Racca
Co-Investigators /
Co-Supervisors
Institution Newcastle University
DepartmentNeurology Neurobiology and Psychiatry
Funding typeResearch
Value (£) 226,225
StatusCompleted
TypeResearch Grant
Start date 09/01/2006
End date 08/01/2009
Duration36 months

Abstract

The hippocampus plays a key role in learning and memory, and has long served as a model for the cellular basis of synaptic plasticity. Fast excitatory transmission in the hippocampus is mediated by AMPA-type glutamate receptors, and changes in AMPAR composition are involved in synaptic plasticity at hippocampal synapses. Dendritic targeting and local translation of specific mRNAs is a mechanism that synapses can use to control their strength independently of protein transport from the soma. Indeed, recent functional evidence indicates that dendritic AMPAR subunit mRNA localisation and local protein synthesis may participate in regulating the composition of synaptic AMPARs and, ultimately, the strength of hippocampal synapses. This study will characterise: i) the subcellular somatodendritic distribution of AMPAR subunit mRNAs in hippocampal pyramidal cells (high resolution nonisotopic in situ hybridisation); ii) the spatial relation between AMPAR mRNAs and the dendritic synthetic machinery (ISH with LM/EM immunocytochemistry); iii) the role of synaptic and network activity in mRNA localisation (electrophysiology with ISH and IC). These experiments will provide direct demonstration of the presence of AMPAR subunit mRNAs in the dendrites of hippocampal pyramidal neurons, and support the mechanism of dendritic local synthesis of receptors as a tool for neurons in generating lasting changes at individual synapses.

Summary

unavailable
Committee Closed Committee - Biochemistry & Cell Biology (BCB)
Research TopicsNeuroscience and Behaviour
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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