Grant: Banting Postdoctoral Fellowship Program

The brain monitors changes in body temperature and hydration and triggers appropriate responses to restore balance. Dysfunction in these responses can underlie life-threatening conditions, from heat stroke and dehydration to high blood pressure and heart disease. Body temperature and osmolality (the concentration of all particles dissolved in body fluid) must therefore remain within a narrow range. Because mammals use evaporation to cool the body, temperature and fluid balance must be coordinated; for example, salt intake lowers body temperature to minimize the need for sweating (which causes water loss). Despite the importance of coordinating body temperature and hydration, it is currently unknown how the brain achieves this coordination, limiting our ability to optimize treatment of related health conditions. To investigate the brain circuits that coordinate body temperature and hydration, we will use cutting-edge techniques to manipulate the activity of specific neurons and examine the electrophysiological properties of neural circuits. Within the hypothalamus, the organum vasculosum lamina terminalis (OVLT) contains specialized "sensor" neurons that detect temperature and osmolality. These send signals to neurons in the paraventricular nucleus (PVN), which are "effector" neurons known to regulate thermogenesis and fluid balance. We hypothesize that this OVLT-PVN neural circuit orchestrates the coordination of body temperature and hydration. By defining how the brain responds to changes in temperature and osmolality, this project will shed light on how environmental factors affect our physiology - for example: how does heat exposure reduce urination? How does salt intake lower body temperature? And how does exercise in the heat suppress appetite? By identifying the brain circuits underlying these processes in males and females, this research will also provide guidance to optimize treatment of fluid imbalance and dysregulated thermoregulation in men and women.