Thirst neurons anticipate the homeostatic consequences of eating and drinking

• Published in: Nature (London) Vol. 537; no. 7622; pp. 680 - 684
• Main Authors: Zimmerman, Christopher A., Lin, Yen-Chu, Leib, David E., Guo, Ling, Huey, Erica L., Daly, Gwendolyn E., Chen, Yiming, Knight, Zachary A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.09.2016; Nature Publishing Group
• Subjects: 13/51; 14/35; 631/378/1488/1562; 631/378/3920; 64/60; 9/10; 9/74; Animals; Blood; Calcium - metabolism; Drinking - physiology; Eating - physiology; Feedback, Physiological; Female; Homeostasis; Humanities and Social Sciences; letter; Male; Mice; Mouth - innervation; Mouth - physiology; multidisciplinary; Neural Pathways; Neurological research; Neurons; Neurons - physiology; Optogenetics; Physiological aspects; Physiology; Rodents; Science; Studies; Subfornical Organ - cytology; Subfornical Organ - physiology; Thirst - physiology; Time Factors; Water; Water consumption; Water-Electrolyte Balance - physiology; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature18950

Feedback from the oral cavity to thirst-promoting neurons in the subfornical organ (SFO) during eating and drinking is integrated with information about blood composition, providing a prediction of how oral consumption will affect fluid balance and leading to changes in behaviour. Neural circuits driving anticipatory thirst It is vital for mammals to maintain their internal water equilibrium. The neurobiological mechanisms linking thirst response behaviour and fluid balance maintenance raise intriguing questions, given that these two components operate on different timescales. Two papers in this issue of Nature identify areas of the mouse brain that respond to and anticipate thirst. Zachary Knight and colleagues reveal a role for thirst-promoting neurons in the subfornical organ (SFO). During eating and drinking, feedback from the oral cavity to the SFO—one of the three sensory circumventricular organs of the brain—is integrated with information regarding blood composition, providing an indication of how oral consumption is likely to alter fluid balance, leading to behavioural adjustments. Charles Bourque and colleagues identify a projection from central clock neurons that drives anticipatory water intake just prior to sleep, regardless of physiological need. Without this specifically timed increase in water intake, animals suffered from dehydration near the end of a period of sleep. Thirst motivates animals to drink in order to maintain fluid balance. Thirst has conventionally been viewed as a homeostatic response to changes in blood volume or tonicity 1 , 2 , 3 . However, most drinking behaviour is regulated too rapidly to be controlled by blood composition directly, and instead seems to anticipate homeostatic imbalances before they arise 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 . How this is achieved remains unknown. Here we reveal an unexpected role for the subfornical organ (SFO) in the anticipatory regulation of thirst in mice. By monitoring deep-brain calcium dynamics, we show that thirst-promoting SFO neurons respond to inputs from the oral cavity during eating and drinking and then integrate these inputs with information about the composition of the blood. This integration allows SFO neurons to predict how ongoing food and water consumption will alter fluid balance in the future and then to adjust behaviour pre-emptively. Complementary optogenetic manipulations show that this anticipatory modulation is necessary for drinking in several contexts. These findings provide a neural mechanism to explain longstanding behavioural observations, including the prevalence of drinking during meals 10 , 11 , the rapid satiation of thirst 7 , 8 , 9 , and the fact that oral cooling is thirst-quenching 12 , 13 , 14 .