The long term goal for this project is to describe the cellular mechanisms that regulate the formation and maintenance of synaptic connections between neurons. In this study the interaction of chick sympathetic preganglionic neurons with their normal target cells, neurons from the sympathetic chain ganglia will be explored. Experiments will use cell culture, because in culture the number of cells, type of cells and media in which the cells grow are under experimental control, and because neurons in culture are accessible for detailed physiological and anatomical observation. The major experimental techniques to be used are intracellular recording and stimulation, and detailed microscopic observation, including cell counting and time lapse observation. During this grant period the five major aims will be: 1) To characterize the time course of synapse formation and the probability that physical contacts between preganglionic neurons and ganglion neurons become synapses. 2) To characterize the way that the growth of a preganglionic axon is changed by contact with cells of defined types. All of the cell types to be examined might normally be encountered by a growing preganglionic axon. 3) To determine whether a trophic factor produced by sympathetic ganglion neurons supports the survival of preganglionic neurons. 4) To examine the relationship between the structure and function of recently formed synapses. 5) To determine whether connections between preganglionic neurons and sympathetic ganglion neurons are regulated by competitive interactions. Each of these projects is aimed at understanding a different crucial aspect of the formation or maintenance of synaptic connections. A defect in any one of the developmental steps could create a highly disordered nervous system. These studies thus are directly relevant to understand disorders of the development of the nervous system. Defects in the cellular interactions involved in synaptic maintenance are also likely to be the cause of some neurological disorders.
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