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.
The overarching aim of this proposal is to uncover the function of basal forebrain cholinergic signaling on hypothalamic hormone physiologies and release. We recently discovered novel neuronal projections from the basal forebrain to the median eminence of the hypothalamus. When we increase the cholinergic tone of these projections, we uncovered a dramatic hormone-driven weight loss phenotype. Here we propose to test the hypothesis that Cholinergic signaling from the basal forebrain modulates hypothalamic hormone release. By testing this hypothesis, our goal is to better understand neuroendocrine physiology regulation and the pathologies that arise when this system is perturbed.
| Liu, Gary; Patel, Jay M; Tepe, Burak et al. (2018) An Objective and Reproducible Test of Olfactory Learning and Discrimination in Mice. J Vis Exp : |
