Energy homeostasis requires the orchestration of autonomic, somatic, and endocrine responses. Data from a number of laboratories have shown that this control, in part, is mediated by caudal brainstem mechanisms and not exclusively by forebrain systems as once thought. This application describes experiments that will further reveal interoceptive and integrative caudal brainstem mechanisms that contribute to the integrated neural system controlling energy homeostasis. Fourth ventricular phlorizin stimulates feeding but not sympathoadrenal hyperglycemia, whereas 5-thioglucose stimulates both responses. These data suggest that different metabolic and/or caudal brainstem systems control these compensatory responses. This dissociation will be replicated and extended by the 4th ventricle application of phloretin, a structurally and functionally related drug to phlorizin. These metabolic interoceptors may be an afferent limb for the ingestive behavior triggered by food deprivation and hypoglycemia in chronically decerebrated rats. To test this hypothesis, intraoral sucrose intake and taste reactivity ingestive and aversive response sequences will be measured in decerebrated rats following 4th ventricular 5-thioglucose. The effects of area postrema lesions on the interoception of metabolic signals and integration with taste information to control the rat's response to tastes (palatablity) will be assessed by measuring intraoral sucrose intake and taste reactivity responses. To determine whether the effects of area postrema lesions on the neural control of taste palatabilty are mediated by the local circuitry of the caudal brainstem, intraoral intake and taste reactivity responses elicited by orally infused tastants will be measured in area postrema lesioned decerebrated and nondecerebrated rats. The participation of the area postrema in the caudal brainstem control of compensatory sympathoadrenal hyperglycemia will be evaluated by measuring plasma glucose in area postrema lesioned and pair-fed intact rats following 4th ventricle and systemic 5-thioglucose injection. Collectively, these data will reveal caudal brainstem controls over energy homeostatic responses and whether caudal brainstem neural circuitry alone is sufficient for their production; thereby further deciphering the organization of a motivated, regulated system such as feeding and energy balance.
