Over the past thirty years, our understanding of hypothalamic regulatory mechanisms and function has expanded enormously. Despite these advances, the link between structure and activity remains, for the most part, a matter of hypotheses and conjecture. Recent advances in molecular biology suggest that c-fos, an oncogene product, is induced in neurons after stimulation. This proposal seeks to explore the relationship between cellular activity and expression of c-fos using double-labeling immunocytochemistry in the magnocellular and parvocellular hypothalamus. The proposed experiments will describe under carefully controlled conditions, the time course and dose-response characteristics of stimulated c-fos expression. Specifically, the magnocellular neurohypophysial system will serve as a model for establishing the relationship between neurosecretory response to stimulation (i.e., vasopressin and/or oxytocin secretion) and the presence of immunoreactive c-fos in vasopressin and oxytocin neurons. The remaining experiments utilize c-fos expression to identify functional subpopulations of active neurons in anatomically related groups of neurons within the magnocellular and parvocellular hypothalamus. Functional anatomy of the magnocellular system will be analyzed by observing the patterns of c-fos induction after well known physiological (osmotic stimulation, hypotension, hypovolemia, gastric distension, suckling) and pharmacological (CCK, angiotensin H) stimuli. For parvocellular functional anatomy, c-fos immunoreactivity evoked by anorexigenic stimuli (such as gastric distension, CCK, bombesin, fenfluramine, and lithium chloride) will be localized in oxytocin and CRF neurons to define the functional circuitry involved in the hypothalamic regulation of gastric function. The proposed studies will add a new dimension of analysis to further our understanding of the relationship between structure and function in the mammalian central nervous system.
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