THE VISCERAL NEURAXIS IN HOMEOSTASIS

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The visceral neuraxis of the mammalian brain is a network of neural connections that mediates the behavioral and physiological controls of homeostasis. It can be defined neuroanatomically by its connections to the autonomic nervous system, connections with circumventricular organs of the brain and connections to the major hypothalamic nuclei affecting endocrine function as well as by interconnections of intervening nuclei. The circumventricular organs, which lack a blood brain barrier making them putative central receptor sites for humoral factors affecting visceral function, and the visceral afferents (chemoreceptors, baroreceptors and mechanoreceptors) of the peripheral nervous system make up the sensory side of the network. The motor components are the autonomic nervous system, endocrine system and homeostatic behavior. The long term objectives of this project are to define and understand the operation of the components of the visceral neuraxis contributing to the generation of ingestive behaviors and specific behavioral states and the factors which convert them into health damaging behaviors or states that accompany obesity, schizophrenia, hypertension, psychogenic polydipsia, stress ulcers, and essential hypernatremia. The first specific objective is to complete the viscerotopic mapping and immunocytochemical characterization of the brainstem's innervation of organs of the alimentary canal. Neuroanatomical studies (single and double labeling) at the light and electron microscopic level will be done using conjugates, particularly cholera toxin, of horseradish peroxidase, fluorescent dyes, dye tagged lectins, toxins and antibodies to neuropeptides. The goal is to determine how incoming visceral afferent information is routed and modified by neuropeptides for local control of viscera and for influencing behavior. The second goal is to determine at the ultrastructural level how gastric afferents which presumably play a role in satiation distribute to neurons that project up the visceral neuraxis and to neurons that remain connected locally. The third goal is to determine at the ultrastructural level using a double labeling technique how descending projections from the hypothalamus to the vagal complex influence the input and processing of visceral afferent information through the visceral neuraxis for use in behavior. The fourth goal is to determine the effects of microlesioning pathways and terminal field sites of new projections from the subfornical organ on drinking behavior and renal function in response to thirst challenges.