The overall objective of the proposed multidisciplinary research is to determine the basic physiologic signaling processes mediating brainstem mechanisms involved in coordinating neural, endocrine and behavioral determinants of nutrient homeostasis and ingestive behavior. Specifically, the proposed research will focus on brainstem mechanisms mediated by the nucleus of the solitary tract (NTS) - its central role as an integrating site in the brainstem for coordinating neural and humoral nutrient-related signals with the consequent production of appropriate viscerobehavioral response patterns. Our general hypothesis is that the integration of nutrient-related information and the coordination of appropriate homeostatic response patterns by the NTS occurs at both the afferent limb and the efferent limb of the neural organizational network mediating feeding behavior, nutrient homeostasis and metabolic regulation. The 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 feeding behavior. Thus, our specific hypotheses are that the NTS subserves the following multiple roles in nutrient homeostasis: (1) a chemosensory role for nutrient-related signals in the blood or CSF, likely mediated via its association with the area postrema (AP); (2) an integrative role for coordinating visceral sensations mediated by both neural and humoral signals 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 feeding behavior. The two Black American and three White American scientists who work on this project, will employ a multidisciplinary and collaborative research strategy with investigators working cooperatively so that NTS-mediated mechanisms of nutrient homeostasis can be simultaneously examined at multiple levels of analysis - from events occurring at the cellular and tissue level to relatively complex appetitive responses at the behavioral level.
