Gastrointestinal secretory and motor functions are markedly altered in response to various environmental stressors and to changcs in behavioral arousal. It follows that the brain regions responsible for interpreting the significance of events external to the organism might also modiate thc changes in gastrointestinal function. Several forebrain nuclei are thought to be involved in the adjustment of thc """"""""internal milieu"""""""" to support changes in behavior demanded by the environment. Three of these structures will be addressed in this proposal: the paraventricular nuctcus of the hypothalamus (PVN), the central nucieus of the amygdala (CNA), and the bed nucleus of the stria terminalis (BST). Available anatomical and physiological evidence indicates that all of these brain regions send direct, monosynaptic input to the brainstem vagal nuclei, which are critical in the parasympathetic control of the gastrointestinal tract. In addition, the nucleus raphe obscurus (nRO), which may bc part of a ncural circuit controlling the production and maintenancc of the sleep-walking cycle, also maintains a direct connection with the vagal nuclei. Immunocytochemical studies have identified those four structures as sources of peptidergic innervation of the vagal sensorimotor nuclei. Recent physiological studies imply that many of the peptides contained within these sources of input to vagal neurons significantly alter gastrointestinal function. Our goal is to establish specifically how these peptide-containing pathways influence the activity of identifiable components of the vagal circuits which control gastrointestinal function. We will pursue this goal by using electrophysiological and gastroenterological methods in combination with a technique for quantitative micropressure injection of peptides (and their antagonists) into physiologically-identified clusters of vagal sensory and motor neurons. By applying these methods, we may begin to elucidate the details of central peptidergic modulation of brainstem circuits which control the gastrointestinal tract. Such information will be essential to ultimately understand how the brain is implicated in dysfunctional states such as diarrhea, constipation and ulcer.
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