The objectives of this proposal are to determine neural substrates in the rodent hindbrain through which gustatory stimuli guide ingestive behavior. The regulation of ingestive behavior is exceedingly complex, involving widespread regions of the central nervous system but the basic regulatory function of taste to determine palatable from unpalatable stimuli is complete in the caudal brainstem. These consummatory behaviors of ingestion and rejection are essential to the homeostatic control of energy balance. Anatomical studies suggest that the lateral tegmental field of the medullary reticular formation is a multifunctional substrate, receiving afferent sensory signals from the gustatory region of the nucleus of the solitary tract and producing the appropriate oromotor patterns of ingestion or rejection. When this region is pharmacologically inactivated, taste-elicited ingestion and rejection reponses are eliminated. The proposed experiments combine several techniques to address two broad questions: the generality and spatial extent of the brainstem consummatory substrate and its underlying mechanisms. Increasing appetitive responses to different stimuli by pharmacological infusions into selected forebrain sites will be combined with reversible block of selected brainstem reticular formation sites to establish whether forebrain signals converge on a single hindbrain region. A second series of microinfusion studies will determine the role of inhibitory amino acids and nitric oxide on oromotor coordination and a related series of studies will use double-labeling immunohistochemistry combined with retrograde transport and expression of the immediate early gene c-fos produced by gustatory stimulation to identify the source of these neurotransmitters and their respective receptors on interneurons in the circuit. Diseases such as obesity, hypertension, anorexia nervosa and dysphagia all involve ingestive dysfunction. Understanding the neurological basis of the fundamental biological decision ingest or reject food will contribute to the eventual solution of these chronic debilitating disorders.
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