The goal of this research is to determine the basic neuroreceptor signaling processes of nutrient homeostasis mediated by the nucleus of the solitary tract (NTS) for coordinating neural and humoral nutrient-related signals with the consequent production of appropriate autonomic and viscerobehavioral response patterns. Our general hypothesis is that the integration of nutrient-related information and the coordination of autonomic response patterns by the NTS occurs at both the afferent and efferent limbs of the neural organizational network mediating ingestive behavior, nutrient homeostasis and metabolic regulation. Our general hypothesis exploits the observation that the NTS is not only the principal recipient site in the CNS of first-order afferent input from the vast array of visceral sensory receptors involved in nutrient homeostasis, but the NTS also has extensive direct reciprocal connections with virtually all structures at every level of the neural axis involved in nutrient homeostasis, metabolic regulation and ingestive behavior. Thus, the specific aim of the proposed research is to determine the neuroreceptor signaling processes by which the NTS subserves the following multiple roles in nutrient homeostasis: (1) a chemosensory role for nutrient-related signals in the blood or CSF: (2) an integrative role for coordinating visceral sensations transmitted to the NTS mainly via the vagus nerve: (3) a major role as an autonomic control center in the brainstem for the production of """"""""short-loop"""""""" homeostatic response patterns and (4) an effector role for some components of ingestive behavior. The overall research strategy employs two dimensions of experimental analysis which can be powerfully coordinated: (1) analysis at the tissue level - in vitro studies with the NTS slice preparation to examine the modulation of monoamine release by nutrient-related signaling substances including transmitters., hormones, nutrients and neuropeptides and (2) analysis at the physiological systems level - in vivo microinjection studies in the NTS to examine the modulation of viscerohumoral and autonomic response patterns elicited by application of nutrient-related signaling substances. These studies will provide an integrated, multidisciplinary spectrum of research experiences and research training opportunities in the neurosciences for MBRS student participants at both the undergraduate and graduate levels. Students will participate in all aspects of the research and contribute to an overall understanding of NTS-mediated mechanisms of nutrient homeostasis.
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