Basal Forebrain Cholinergic Modulation of Hypothalamic Hormone Release

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Project Abstract Hypothalamic hormones regulate multiple physiologies, and changes in their signaling to a variety of pathologies including obesity, growth and metabolic abnormalities, and sexual dysfunction. Prominent neuroendocrine pathways that regulate physiologies of metabolism, growth, and stress, all rely on hypothalamic input for their control. Little is known about extra-hypothalamic inputs that control these pathways. Towards this goal, we have discovered a novel projection from the basal forebrain cholinergic system to the hypothalamus and median eminence. Furthermore, we have shown that an increase in the activity of these cholinergic neurons leads to a novel hormone-driven weight loss phenotype. Using innovative techniques in conditional viral genetics, cell-type specific neuronal manipulations, cell-type specific labeling, optogenetics, and ultrastructural imaging we propose to determine the role of basal forebrain cholinergic signaling on hypothalamic hormone release. Specifically, we propose to (1) determine which hypothalamic- pituitary axis hormones are altered by changes in cholinergic tone and (2) determine how cholinergic signaling alters the release of hypothalamic hormones.