Functional mapping of thirst circuits in the aging mouse brain

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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 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 and optogenetic techniques in awake behaving mice. 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.