To understand how the nervous system controls complex motor acts, we must identify the neural and muscular elements that contribute to a particular act, define their electrical properties, and determine their interconnections. For a few behaviors in invertebrates this has been possible. These control systems are not static; neuromodulatory influences constantly tune both the neural and muscular components of these systems to meet the demands of the animal's changing environment. We must now explore these tuning mechanisms, if we are to further our understanding of how neural and muscular systems produce environmentally relevant behavior. We are more likely to achieve this goal, if we concentrate our efforts on the well-defined behavioral control systems of invertebrates. The well-studied heartbeat control system of the leech includes a central pattern generating network of heart interneurons, that elaborate a pattern of rhythmic activity which is imposed on heart motor neurons and modulatory neurons. The motor neurons then impose their rhythmicity on the heart by entraining the heart's myogenic rhythm, while the modulatory neurons modulate the myogenic properties and the contractile strength of the heart. Not only are the hearts subject to modulation, but a variety of identified sensory and motor pathways modulate the period of the central pattern generator. Thus at each level within the control system, modulatory influences can be ascribed to identified neurons. We have recently demonstrated that the neuropeptide, FMRFamide, modulates the heartbeat control system both peripherally and centrally and it is contained in several of the neurons that accomplish this modulation. We propose to study modulatory influences on the heartbeat control system and other motor systems in the leech, with particular emphasis on the modulatory role of FMRFamide. We will attempt to identify the modulatory neurons and substances involved and to characterize their mode of action in terms of the specific membrane currents they regulate. By studying the action of peptide and other neuromodulators in the leech we will uncover important information about the role of neuromodulators in the nervous system, that can provide insights into the pharmacological bases of neural disorders.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Neurology B Subcommittee 2 (NEUB)
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Emory University
Schools of Arts and Sciences
United States
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