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The effects of acute stress on glutamate receptor trafficking and synaptic plasticity in the hippocampus

Reference	BB/G003963/1
Principal Investigator / Supervisor	Professor Kwangwook Cho
Co-Investigators / Co-Supervisors	Professor Graham Collingridge, Professor Stafford Lightman
Institution	University of Bristol
Department	Henry Wellcome LINE
Funding type	Research
Value (£)	560,288
Status	Completed
Type	Research Grant
Start date	05/01/2009
End date	04/01/2012
Duration	36 months

Abstract

It is of great evolutionary advantage for animals to adapt rapidly to a changing and challenging environment, and in particular for an animal to have a stress-responsive neuroendocrine system that can focus the animal's vigilance and strengthen the ability to remember critical information related to the stressful event. Whereas the effects of acute stress are of clear adaptive value to the animal, the cellular effects of chronic stress appear to be maladaptive with negative effects on mood and cognition both in rodents and man. In this application we intend to investigate the changes in synaptic function that occur during the early phase of the acute stress response. In particular we shall be looking at alterations in synaptic transmission and synaptic plasticity (long-term potentiation and long-term depression) in the hippocampus. We will investigate molecular mechanisms that regulate the function of AMPARs and NMDARs in these processes and how these are altered both by the acute application of corticosterone in vitro, and ex-vivo following exposure of a rat to an acute stressor.

Summary

The ability of an animal to adapt to a changing environment is critically important for its survival. A very important aspect of this is the ability of the central nervous system to respond to periods of stress. During the initial acute response to a stressor the animal needs heightened vigilance and the ability to focus its attention, energy and cognitive functions on interpreting and responding to the perceived danger. Following this acute response phase the animal needs to tune down its aroused state and store appropriate memories of the event for future reference should similar dangers recur. If the animal continues to be subjected to repeated or prolonged stresses - particularly if they have been unpredictable and the animal has little or no ability to control or avoid them - the stress responses become maladaptive and result in loss of cognitive function and is associated with both physical and psychological disorders. In this application we intend to investigate the changes in synaptic function that occur during the early phase of the acute stress response / the time of heightened vigilance.

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	Neuroscience and Behaviour
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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