Functional mapping of thirst circuits in the aging mouse brain

项目摘要/摘要 液体动态平衡，即维持血液和间质液体中的体积和渗透压，是生命所必需的。 衰老涉及体液平衡的破坏，通常伴随着口渴和饮酒减少。 行为。因此，脱水是老年人的主要健康风险之一，使他们暴露在更高的 罹患糖尿病、心脏或肾功能衰竭、意识减退或丧失的风险，从而 大大增加了它们的死亡率。然而，口渴和饮酒行为的机制随着 人们对年龄的增长知之甚少。流体动态平衡主要受体内结构的调节 下丘脑被称为穹隆下器官(SFO)，它通过直接接触到 体循环。最近，SFO内的一个特定的神经元群体被证明既是 这是规范饮酒行为的必要条件和充分条件。在这里，我建议系统地研究 利用纤维光度法、显微内窥镜和光遗传学技术在清醒状态下改变口渴回路 并将其与生理测量配对。了解口渴回路的功能 随着年龄的变化，我们将扩大对液体失衡和相关疾病进行干预和治疗的能力 老年人的疾病。

PROJECT SUMMARY/ ABSTRACT Fluid homeostasis, the maintenance of volume and osmolality in blood and interstitial fluid, is essential for life. Aging involves breakdown of fluid homeostasis, and is often accompanied by reduced thirst and drinking behavior. As a result, dehydration is one of the major health risks in older individuals, exposing them to higher risk for developing diabetes mellitus, heart or kidney failure, or reduced or loss of consciousness, and thereby greatly increasing their mortality. However, the mechanism by which thirst and drinking behavior changes with advancing age is very poorly understood. Fluid homeostasis is primarily regulated by a structure in the hypothalamus called the subfornical organ (SFO), which monitors the state of fluid balance via direct access to systemic circulation. Recently, a specific population of neurons within the SFO was shown to be both necessary and sufficient for regulating drinking behavior. Here I propose to systematically investigate how the thirst circuit changes with aging, using fiber photometry, microendoscopy and optogenetic techniques in awake behaving mice and pair this with physiologic measurements. Understanding how the function of the thirst circuit changes with age will expand our ability to develop interventions and treatment for fluid imbalance and related illnesses in the elderly.