Neural and cellular basis of fluid homeostasis during hibernation

Yale University, New Haven CT

Investigators

Abstract

Mammalian hibernation is fascinating. During a short period of time, hibernating animals undergo dramatic adaptive changes, including reduction in heart and respiration rate and decrease of core body temperature from 37°C (98.6°F) to 4°C (39°F), yet they do not experience cold-induced pain, and their organs continue to function despite being cold, non-functional, and deprived of oxygen for eight months out of the year. Moreover, during hibernation, animals do not drink; therefore, hibernators must rely solely on the management and utilization of internal resources for long-term survival. This project seeks to understand the molecular mechanisms that allows hibernators to survive for months without water, using a range of cutting-edge tools and approaches not been previously used for hibernation research, such as optogenetics and fiber photometry. The outcomes of this study will have broad scientific implications, including a better understanding of general mechanisms that regulate internal water and ionic balance common to all mammals. This project also involves educational and outreach efforts in the context of an extracurricular educational program (Sensory Physiology Club) that promotes scientific knowledge in human and animal physiology among school students from middle- and high schools from Connecticut, New York, and Massachusetts. The efforts are designed to spark interest in biological science through lectures and interactive experimental activities that go beyond the science curricula of most schools. The main scientific goal of this study is to broaden our limited understanding of fluid homeostasis in mammals at the cellular, molecular, and circuit levels by studying ground squirrels during hibernation. This project tests the hypothesis that ground squirrels endure long-term water deprivation in part by modifying the hypothalamic axis, which controls thirst and mediates the release of antidiuretic hormones. Specific aims of this proposal include investigation of the neuronal mechanisms that support the release of vasopressin and oxytocin from the posterior pituitary, and suppress water-seeking behavior during hibernation. This project combines cellular, molecular, and organismal levels of research and uses tools and approaches from a spectrum of disciplines: state-specific biochemical analysis of neuropeptides and hormones, quantitative analysis of hormonal production, differential transcriptomics, electron microscopic and morphometric analyses of hormonal release, and behavioral analyses of drinking behavior. A major innovative aspect of this project is the use of optogenetics, fiber photometry, and electrophysiological tools, which have not been used previously with hibernating animals. The outcomes of this study will delineate general principles of fluid-ionic balance fine-tuning, suggest a strategy to sustain life when water is unavailable, and predict whether hibernation can be induced in other mammals. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.