The long-term goal of the proposed work is to characterize at high resolution the structure and chemistry of circuits in the mammalian brain that underlie the basic drives that keep individual animals alive and assure perpetuation of the species associated with hunger and thirst, defensive behavior, reproductive behavior, and the sleep/wake cycle. Previous neuroanatomical work has clarified the input/output relationships and neurotransmitters of medial hypothalamic subsystems mediating each of these broadly defined functions, and has shown that they-along with closely associated limbic telencephalon regions-project topographically to the lateral hypothalamic area (LHA). Functional evidence suggests that the LHA plays an important role in positive reinforcement, behavioral arousal, and various aspects of motivated behavior, although the topographic organization of its neural inputs and axonal projects is poorly understood. The proposed work is based on the hypotheses that the LHA has two functionally and structurally distinct zones related to behavioral state, and the ventral zone being divided into 20 or more distinct cell groups or nuclei related to specific functional systems.
Three specific aims based on the use of experimental neuroanatomical methods in the rat are designed to explore this hypotheses: (1) A systematic computer graphics atlas/database of LHA differentiation based on connections and in situ hybridization-related mRNA expression will be elaborated. (2) Projections of cell groups in the dorsal and ventral regions will be determined and compared. And (3) neuronal cell types (phenotypes) in these regions will be determined using combined axonal transport/hybridization histochemical methods. This analytical/synthetic approach is designed to provide a structural framework for the rational design of functional experiments, as well as provide new insights into, and eventually treatments for, diseases that involve forebrain neural systems controlling, eating, drinking, aggression and defense reproduction, the sleep-wake cycle, and presumably mood disorders as well.
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