NEURAL PATHWAYS FOR METABOLIC CONTROL OF INGESTION

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DESCRIPTION: This application for support of work examining the mediation of two distinct metabolic controls on food intake, glucoprivic and lipoprivic controls. Prior work by the investigator has demonstrated different sites for activation of glucoprivic and lipoprivic feeding: glucoprivic controls appear to be located in the hindbrain and lipoprivic controls depend upon receptors associated with abdominal vagal sensory neurons. The proposal has three specific aims. The first aim is to precisely localize hindbrain glucoreceptor neurons that mediate glucoprivic feeding. Experiments addressing this aim map hindbrain sites at which feeding behavior can be elicited by nanoliter injections of glucoprivic agents. Experiments also asses the effects of lesions of apparent glucoreceptive cell groups on the ability of 5TG to elicit of food intake and fos expression. The second aim is to identify the specific neuronal pathways responsible for transmission of sensory information crucial for elicitation of both glucoprivic and lipoprivic feeding from hindbrain to forebrain sites. Experiments addressing this aim will utilize c-fos immunohistochemistry to identify retrogradely labeled neurons that are activated by glucoprivation or lipoprivation and by examining the feeding response and fos expression to glucoprivic and lipoprivic agents in rats in which aspects of these neural pathways have been lesioned. In addition, under this aim, nutrients that block lipoprivic feeding will be systemically infused to examine their effect on fos expression at various levels of the identified neural system mediating lipoprivic feeding. The third aim of the project is to identify the neurotransmitter phenotype of the neurons mediating glucoprivic and lipoprivic feeding. Hindbrain catecholamine cell groups will be examined for expression of fos in response to glucoprivation. In addition, glucoprivic feeding and induction of fos in the brain will be studied following lateral ventricular injections of 6-hydroxydopamine to determine the necessity of catecholamine mediation. Finally, a potential role for the neuropeptide galanin in lipoprivic feeding will be examined. The investigator has previously demonstrated that a galanin receptor antagonist microinjected into the fourth ventricle reduced lipoprivic feeding. This result will be extended by studying effects of microinjections of galanin and a galanin antagonist in specific brain sites important for lipoprivic feeding. Thus, the overall goals of this project are to 1) identify neuronal populations involved in glucoprivic and lipoprivic feeding, 2) identify the local neurotransmitters on which these responses depend and 3) identify how the actions of these neuronal populations are modified under different metabolic states.