The long-term goal of this research program is to contribute to the understanding of the role played by peptides in processing information within the central nervous system (CNS). The granting of a Research Career Development Award (RCDA) will provide the applicant with the opportunity to develop his career in three major ways: 1. to integrate neuroanatomical and neurophysiological perspectives through first skills and expertise, specifically those related to the electrophysiological techniques of patch clamping and to the anatomical techniques of EM immunocytochemistry; 3. to gain additional analytical skills, specifically in the use of the computer to acquire, analyze and interpret electrophysiological and anatomical data. In support of this application, the applicant's institution is prepared to relieve the applicant of major teaching and University- wide committee responsibilities during the five-year career development period so that time may be devoted fully to research- related activities and to the acquisition of the necessary skills. This RCDA application proposes to conduct a morphophysiological analysis of peptidergic neurons using the rat retina as a CNS model. While it is generally accepted that peptides have neurotransmitter-related roles, relatively little is known about their influences on neuronal function and the elucidation of peptide-mediated effects on neurons remains a pressing issue in the study of CNS neurotransmitters. The focus will be on the corticotropin releasing factor (CRF) and vasoactive intestinal polypeptide (VIP) systems in the retina at the ultrastructural level using EM immunocytochemistry and 2) to assess CRF and VIP actions on membrane properties of identified, solitary retinal neurons using a combination of intracellular and whole-cell voltage clamp recordings. The overall hypothesis is that the synaptic layout of the CRF and VIP systems in the retina is consistent with them having a neuromodulatory role, modulating the excitability of postsynaptic neurons.
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