Our long term goals are to understand peptide neurotransmitter mechanisms that underlie modulation of neuronal activity, and the contributions of these mechanisms to regulation of complex behavior. We use as an example the marine mollusk Aplysia, which permits detailed analysis at the cellular and molecular levels using combined electrophysiological and behavioral techniques. The bag cells are a group on neuroendocrine cells that initiate egg-laying, a complex behavior that lasts for up to several hours. The bag cells release four peptides, derived from a common precursor protein, that act as transmitters in the central nervous system to modulate activity for up to several hours. We recently purified and identified a novel peptide that is homologous to the vertebrate peptide family that includes neuropeptide Y and pancreatic polypeptide. It mimics one of the modulatory actions of the bag cells, prolonged inhibition of target neurons in the abdominal ganglion. Our investigations have two main foci: to establish novel physiological roles of neuropeptides and to test further the hypothesis that the central actions of the bag cells, and neurons like them in other parts of the central nervous system, are important for regulation of complex behavior during eg laying. We want to identify the transmitter mediating prolonged inhibition, for which the neuropeptide Y-like peptide is a strong candidate. We will describe further the nerve pathways and neurons that lead to activation of the bag cells and initiation of egg laying. We propose experiments to identify neurons and motor systems in the head ganglia that are modulated by application of bag cell peptides and determine whether they are also modulated by activation of the pathway that initiates egg laying. Further, we will describe the development of peptidergic actions produced by the bag cells during reproductive maturation from juvenile to adult. We will investigate additional physiological roles of the neuropeptide Y-like peptide, and two other novel peptides we have been chemically characterizing, in other parts of the nervous system and in control of behavior. These investigations may result in a clearer understanding of fundamental mechanisms of chemical signalling between neurons, particularly a) the functional consequences of co-transmission mediated by neuropeptides, b) the evolution of structure and function of neuropeptides, c) the detailed cellular mechanisms by which modulation of neuronal activity by neuropeptides for prolonged periods can contribute to regulation of complex behavior, and d) the development of peptidergic neurotransmission during reproductive maturation.
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