The proposed research is a continuation of ongoing studies of the role of the cellular milieu in regulating neuronal growth and development. The studies will focus on defining mechanisms regulating neurotransmitter and receptor phenotypic expression, and on determining how presynaptic transmitters are matched to appropriate postsynaptic receptors to form a functional synapse. The rat sympathetic superior cervical ganglion and its target tissues in culture will be used to examine the regulation of cholinergic and adrenergic transmitters and receptors. Specifically these studies will: 1. Define the effects on receptor expression of epigenetic factors which regulate neurotransmitter development. In particular, examine the effects of factors which regulate transmitter expression in cultured sympathetic neurons on receptor expression in cultured autonomic target tissues. 2. Further define neurotransmitter and receptor ontogeny in neural crest and its derivatives, and characterize factors which regulate the initial expression of transmitters and their receptors. 3. Define mechanisms underlying the effects of cell-cell contact on choline acetyltransferase, tyrosine hydroxylase, and somatostatin transcription and translation. In a broader sense, these studies seek to define the molecular basis of neurotransmitter and synaptic plasticity. It is hoped that these studies may indicate biochemical loci where therapeutic intervention in disease processes may lead to a return to normal neuronal function.
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