This is the second revised application addressing the general question of neurotransmitter/neuropeptide expression in superior cervical ganglion cells. Based both on previous criticism and on additional preliminary findings, the applicant now proposes to use cultured SCG neurons to examine the hypothesis that anterograde signals (represented by PACAP (pituitary adenylate cyclase activating polypeptide) peptides) and retrograde signals (represented by CDF/LIF (cholinergic differentiation factor/leukemia inhibitory factor)) differentially regulate the biosynthesis, content, mRNA and release of specific sympathetic neuron transmitters and neuropeptides through receptor-mediated activation of specific intracellular signaling pathways. Biochemical, molecular and morphological approaches will be used to further 2 specific aims: 1) To examine the mechanism of PACAP presynaptic regulation of SCG neuronal NPY and catecholamine expression, and 2) To investigate CDF/LIF regulation of SCG neurotransmitter and neuropeptide expression and neurophenotypic plasticity. For each of these aims, 4 basic questions will be addressed: 1) Is there differential regulation specific for NPY and catecholamines? 2) What is the cellular basis for the altered expression? 3) What receptors are mediating the actions? 4) What are the intracellular signaling mechanisms regulated by these factors? These studies will begin to delineate the cellular events that guide neuronal transmitter and peptide expression in development, stress, injury and regeneration.
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