The long-term goal of work proposed here is to characterize the structure and chemistry of circuits in the mammalian brain that underlie motivation (or goal-oriented behavior) and emotion (or affective behavior). Previous work indicates that a complex of relatively well-defined cell groups in medial parts of the hypothalamus-the medial zone nuclei-occupy a key position in this circuitry, which is responsible for maintaining the life of an animal (by regulating metabolism) as well as the species as a whole (by controlling reproduction). The proposed experiments are designed to test the hypothesis that medial zone nuclei give rise to a topographically organized, branched, ascending and descending output, with one component ending at least partly in the thalamus, and the other component ending in the brainstem (much like the mammillary body and caudally adjacent reticular part of the substantia nigra).
Three specific aims, all of which are based on the use of experimental neuroanatomical methods in the rat, are designed to explore this hypothesis. (1) The topography of limbic inputs to the medial zone from the basal amygdala, bed nuclei of the stria terminalis, and lateral septal nucleus will be determined with the PHAL anterograde tracer method. This information will greatly clarify the descending afferent control of medial zone outputs. (2) The extent and topography of branched medial zone projections to the thalamus and brainstem will be examined with retrograde multiple labeling techniques and with serial section PHAL analysis. Wherever feasible, the possible neurotransmitter content of these pathways will be examined with immunohistochemistry and in situ hybridization. And (3) the topography of cortical projections from parts of the thalamus receiving medial zone inputs will be determined with PHAL. The circuitry under consideration may play an important role in the etiology of at least some forms of hypertension, obesity, diabetes, reproductive dysfunction, and clinical depression.
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