The goal of this project is to elucidate in rats the neuropeptide Y (NPY) circuitry and specific receptor subtypes in the hindbrain that may participate in a larger neural network involved in the control of food intake and the regulation of body weight. Most attention given to NPY's role in food intake has focused on the hypothalamus. The hindbrain has received less attention, even though NPY and its receptors are widespread in hindbrain and NPY-related agonists stimulate feeding when their distribution is restricted to the hindbrain. Experimental aims in this proposal focus on hindbrain NPY and NPY receptors and address several questions: Does NPY activity in hindbrain participate in the physiological control of food intake? This question will be pursued using fourth ventricular administration of specific NPY receptor antagonists. Where is the locus, or loci, where NPY acts to stimulate feeding? Based on preliminary results, we hypothesize a locus exists in the dorsal pons central gray area. This locus, we predict, will be more sensitive than other hindbrain sites to microinjections of an NPY- related agonist. What effect do lesions of this sensitive locus have on ad libitum and deprivation-induced food intake? What is the origin of NPY afferents to this locus? Experiments addressing this question will employ retrograde labeling methods combined with immunostaining for NPY. What is the distribution and binding characteristics of the specific NPY receptor subtypes that mediate NPY's effects on food intake? For these experiments we will combine behavioral methods using microinjection of NPY receptor agonists and antagonists with receptor binding methods using quantitative autoradiography. The major emphasis of this proposal is on NPY afferents in the dorsal pons and the locus or synaptic field where NPY acts to stimulate food intake. Towards the long range aim of mapping the larger NPY neural circuitry, I propose additionally to investigate NPY gene expression in response to food deprivation in locus coeruleus and dorsal tegmental nuclei, two dorsal pontine loci with NPY efferent projections to forebrain and perhaps hindbrain targets involved in NPY-stimulated food intake. The hindbrain locus for NPY action in feeding is a doorway through which to approach the broader neural circuitry regulating energy balance. I plan as long term goals to characterize the functional and anatomical relationship between NPY and other neuro- transmitters, and the relationship between hindbrain and hypothalamic neural substrates involved in the control of food and regulation of body weight. Results will contribute to the overall understanding of the neurobiology underlying obesity and eating disorders.
