Basal Forebrain Cholinergic Modulation of Hypothalamic Hormone Release

项目摘要 下丘脑激素调节多种生理学，以及它们的信号传导的变化， 病理学包括肥胖、生长和代谢异常以及性功能障碍。突出 调节新陈代谢、生长和应激生理学的神经内分泌途径都依赖于 下丘脑输入来控制它们。关于控制这些的下丘脑外输入知之甚少 途径。为了实现这一目标，我们已经发现了一个新的投射从基底前脑胆碱能神经 下丘脑和正中隆起。此外，我们还表明， 这些胆碱能神经元的活性导致了新的代谢驱动的体重减轻表型。使用创新 条件病毒遗传学技术，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神经的作用， 下丘脑激素释放的信号。具体而言，我们建议（1）确定下丘脑- 垂体轴激素通过胆碱能张力的变化而改变，并且（2）决定胆碱能信号传导如何 改变下丘脑激素的释放

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.