The central nervous system relies on a vast network of interconnected nerve cells to maintain physiological and behavioral homeostasis. Communication between the cells that comprise neuronal networks is mediated by the regulated secretion of chemical messengers. Through the work outlined in this proposal, we hope to better understand the molecular mechanisms which regulate the secretion of neurotransmitters and neuromodulators from nerve terminals. Our focus is on the proteins which comprise the critical organelle involved in synaptic transmission, the synaptic vesicle. We propose to further characterize molecules specifically localized to synaptic vesicles. Through an understanding of the interactions of these synaptic vesicle proteins with other components of the nerve terminal, we will gain insight into the functions of specific molecules. The availability of recombinant DNA clones encoding synaptic vesicle proteins makes it possible to introduce modified forms of the molecules into cells in culture and to study the resultant phenotypes. Understanding the mechanisms of synaptic transmission, as will be revealed by the experiments proposed here, is critical in defining the underlying defects that give rise to behavioral disorders. This research will aid in the prevention of psychiatric illness and the development of therapies for afflicted individuals.
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