Basal Forebrain Cholinergic Modulation of Hypothalamic Hormone Release

项目摘要 下丘脑激素调节多种生理，并改变其对多种信号的影响 病理包括肥胖、生长和代谢异常以及性功能障碍。突出 调节新陈代谢、生长和应激生理的神经内分泌通路都依赖于 下丘脑的输入用于它们的控制。对控制这些信号的下丘脑外输入信息知之甚少 小路。为了达到这个目标，我们发现了一种来自基底前脑胆碱能神经元的新投射。 系统连接到下丘脑和正中隆起。此外，我们已经表明， 这些胆碱能神经元的活动导致了一种新的激素驱动的减肥表型。使用创新的 条件病毒遗传学、细胞类型特异性神经元操作、细胞类型特异性标记、 光遗传学和超微结构成像，我们建议确定基底前脑胆碱能的作用 下丘脑激素释放的信号。具体地说，我们建议(1)确定哪个下丘脑- 脑垂体轴激素通过胆碱能张力的变化而改变，以及(2)决定胆碱能信号如何 改变下丘脑荷尔蒙的释放。

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.