Research Project
2039098
DESCRIPTION: Recently, a number of synaptic vesicle-proteins have been cloned and their putative roles in regulating synaptic function explored. Several different models for regulation of vesicle motility and fusion have been developed. The characterization of these proteins provides the opportunity to explore, in detail, the assembly of synaptic components during synaptogenesis in vivo. However, little systematic information concerning the developmental expression of these molecules is available. This proposal will examine the normal time course and pattern of expression of synaptic vesicle-associated mRNAs and proteins in the rat superior cervical ganglion (SCG) in vivo. The rodent sympathetic ganglion is an attractive model in which to conduct studies of synaptogenesis, because of its simple organization, accessibility, and the wealth of background information concerning its morphological and physiological development. The developmental expression of synaptic vesicle-associated mRNAs and proteins will be examined in the rat SCG, using in situ hybridization histochemistry and immunohistochemistry. These studies will provide information concerning changes in mRNA and protein expression. The redistribution during development of vesicle proteins from SCG neuronal somata to terminals in target tissues, the iris and pineal, will also be examined. The effect of preganglionic denervation on development of vesicle protein mRNAs in the SCG will be studied to assess the role of transsynaptic regulation of these proteins during development. The following questions will be addressed: When do synaptic vesicle proteins begin to be expressed during development, and how is expression influenced by transsynaptic factors? How are these proteins redistributed during synaptic development? Do patterns of expression of different proteins reflect their proposed functions in the synapse? The working hypothesis is that those synaptic vesicle proteins whose functions are most closely tied will exhibit sequential or coordinate patterns of expression prior to the onset of functional transmission, and will also exhibit similar regulation by transsynaptic factors. Determining whether transsynaptic factors are important for regulating expression of these proteins may have profound implications for synaptic transmission, since assembly of components into complexes appears to be necessary for function. The proposed studies will provide a wealth of information concerning the assembly of synaptic components during synaptogenesis and of possible factors influencing their expression.
