Research Project
6687829
DESCRIPTION (provided by applicant): Feeding and metabolic disorders such as obesity, anorexia, bulimia, gastroesophageal reflux cachexia, dysgeusia, and anosmia contribute to numerous diseases including hypertension, stroke, diabetes, and heart disease, and thus account for a large proportion of health- care costs in North America and other countries. Elucidating the neural mechanisms that control feeding is, therefore, of fundamental clinical significance. Numerous behavioral studies indicate that feeding is regulated by the integration of taste and visceral afferent signals within the central nervous system; however, only a handful of neurophysiological studies have attempted to locate and characterize these mechanisms. This application will evaluate neural interactions between gustatory and visceral afferent signals in the parabrachial nucleus (PBN), a brainstem relay that receives significantly overlapping taste and visceral afferent inputs. The first experiments will use standard neurophysiological recording techniques to test the hypothesis that duodenal nutrient and distension signals are represented in PBN, as they have not been described at this level, and that these signals interact with gastric distension responses. The interaction of duodenal-signals with gastric distension and gustatory responses in PBN will then be neurophysiologically evaluated to test the hypothesis that a concomitant of satiation is expressed in the form of visceral suppression of palatable taste responses in PBN. The final phase of this application will further explore the visceral modulation of PBN taste responses through an attempt to identify whether particular neurotransmitters play a role in mediating the effect. Specifically, neurotransmitter antagonists will be microinjected into the discrete vicinity of single taste cells as they are recorded during visceral and taste stimulation. It is hypothesized that if the suppression of taste responses by visceral stimuli is mediated locally by the neurotransmitter in question, then antagonism of its receptor systems should reverse the taste suppression effect. Identifying the neurotransmitters that participate in the visceral suppression of taste responses in PBN may also provide insight regarding other central mechanisms that participate in feeding control.
