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Presynaptic mechanisms in hippocampal spike timing-dependent plasticity

Reference	BB/H002383/2
Principal Investigator / Supervisor	Professor Ole Paulsen
Co-Investigators / Co-Supervisors
Institution	University of Cambridge
Department	Physiology Development and Neuroscience
Funding type	Research
Value (£)	350,140
Status	Completed
Type	Research Grant
Start date	01/01/2010
End date	31/12/2012
Duration	36 months

Abstract

Long-term changes in synaptic efficacy are important for learning and memory. Such changes, known as synaptic plasticity, are a strong candidate for a cellular mechanism that could underlie memory in the hippocampus. The molecular cascades underlying hippocampal synaptic plasticity have been extensively investigated. In particular, using whole-cell recording, many of the signalling cascades involved in the postsynaptic neuron during induction of long-term potentiation and depression have been elucidated in great detail. Because the presynaptic neuron is more difficult to access directly, there is a relative paucity of strong data on presynaptic mechanisms. With recent technological development, this situation is now changing. New optical techniques can access presynaptic fibres and have made it possible to approach research questions that previously were not feasible, or feasible only with a disproportionate amount of effort. Here we propose to address two fundamental questions that have remained unanswered in hippocampal synapses because they require access to identified presynaptic elements, 1) What is the location of NMDA receptors responsible for induction of hippocampal long-term depression, and 2) what is the influence of the source of input fibres for hippocampal synaptic plasticity? These questions will be addressed using state-of-the-art optical stimulation techniques combined with whole-cell patch clamping. The answers will have implications for our understanding of memory mechanisms in the brain.

Summary

Our brain, as the rest of our body, is made up of two halves, a left brain and a right brain. These halves are almost mirror images of each other, but there are subtle differences in structure and slightly different functions carried out by each half. Whilst it has been known for at least 150 years that, in humans, the left brain and right brain are different, it has only more recently been established that the same holds for brains of simpler animals. In particular, it has been discovered that the mouse brain shows subtle differences in structure between the left side and right side of the brain, and this makes it possible to study the underlying mechanisms and functions with experiments. Here, we propose to investigate possible functions of the differences seen between the two sides of the mouse hippocampus, a structure that is important for memory. We will investigate how easily one can induce changes in the connections between cells, depending on which side of the brain the neurons are located. These experiments will give new insight into lateralisation of function as well as memory mechanisms in the brain.

Committee	Research Committee A (Animal disease, health and welfare)
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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