During neural development many more synapses are formed than are maintained. The long range goal of this research is to understand the mechanisms that determine which synaptic terminals will be maintained, and which eliminated. In this study an in vitro system, which allows for detailed examinations of the organizations and development of synaptic connections, will be used. The major experimental approach will be to use intracellular recording and staining to map the termination of presynaptic neurons onto the surface of dissociated chick sympathetic ganglion neurons, and then to examine in detail the properties of transmission at individual synaptic sites. Cultures will be studied at time points beginning soon after co-culture in order to determine hiw the distribution and the function of terminals change during development. The developmental sequence will be verified by folloiwng individual neurons in long term microcultures. Finally, the growth conditions will be manipulated in order to test possible rules governing synaptic organization. Issues that will be adddressed include the importance of competitive interactions and of pre- and postsynaptic impulse activity. This study will add to our understanding of the steps that lead to stable synaptic transmission. Knowledge of the basic mechanisms that regulate synaptic connections is likely to be relevant to understanding degenerative neurological diseases in which synaptic function is impaired or disrupted.
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