Role of Activity in Refinement of Synaptic Connections

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The goal of this project is to understand how developing nerve cells make connections with muscles, and to determine how those connections alter their properties as a function of activity. There is evidence that developing nerve connections are refined during development by activity mediated mechanisms. The influence of activity on changes in nerve ending size and projection patterns will be examined by use of mutations that disrupt the ability of neurons and muscles to generate normal electrical activity. These changes will also be investigated by the use of toxins that specifically interfere with nerve and muscle electrical activity. To observe the development of the nerve muscle connections, and their responses to experimental manipulations, time-lapse video movies will be made of the living nerve endings maintained in semi- intact cultures. These experiments will elucidate several fundamental features of normal nervous system development.