The goal of this research is to determine how forebrain systems and neuropeptide-defined pathways control the neuroendocrine, autonomic and visceral neural systems in mammals. The short range goals of the research focus on three related issues: (1) How are circadian rhythms regulated in the central nervous systems? The effect of lighting schedule, feeding and drinking schedules, as well as physiological and pharmacological manipulations on the functions of central pacemakers in the albino rat will be studied. Longitudinal assays of overt motor activity, ingestive behaviors and neurophysiological activity will complement cross sectional analyses of opioid peptide levels, opiate receptor binding, metabolism, (by the 2-deoxyglucose method) and ultrastructural changes in hypothalamic regions thought to contain the primary (suprachiasmatic nucleus) and secondary (lateral hypothalamic area, e.g.) circadian pacemakers. The way the body responds to environmental and internal stress, disease states and drug therapy depends heavily on the functions of the circadian rhythm systems, therefore, understanding how these rhythms operate will increase our ability to maximize our own adaptation and survival. (2) In a related series of experiments, opioid peptide systems, especially the dynorphin-containing systems, are investigated for their role in the control of the neuroendocrine, autonomic and visceral neural systems. Preliminary studies suggest that the opioid neural systems are strategically placed to regulate not only circadian rhythms, but also other phylogenetically ancient motor systems related to eating, drinking, digestion, cardiovascular and respiratory control. The studies will aid in our understanding of how peptide systems control these important regulatory functions. The combined immunofluorescence and retrograde fluorescence tracing method will be used to determine connections of dynorphin-(and some enkephalin-) containing neurons in structures that innervate and control and peripheral sympathetic, parasympathetic, and neuroendocrine neural systems. (3) In the third group of experiments, """"""""higher centers"""""""" that may regulate circadian rhythm generators and other motor neural systems will be investigated with new neuroanatomical methodologies. In particular, the efferents of the ventral pallidium to the hypothalamus, hypothalamus to brainstem, and convergence of retinal, ventral lateral geniculate nucleus, dorsal raphe and ventral pallidal inputs to hypothalamus will be studied with anterograde and retrograde techniques which overcome the problem of uptake of tracer by fibers of passage. These studies are important in that they will help elucidate the morphological substrates by which """"""""higher"""""""" and """"""""lower"""""""" brain centers integrate the classical motor systems, circadian rhythms, neuroendocrine systems, pituitary, and autonomic and visceral motor systems of the body.
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