A gut-to-brain signal of fluid osmolarity controls thirst satiation

Christopher A. Zimmerman, Erica L. Huey, Jamie S. Ahn, Lisa R. Beutler, Chan Lek Tan, Seher Kosar, Ling Bai, Yiming Chen, Timothy V. Corpuz, Linda Madisen, Hongkui Zeng and Zachary A. Knight ()
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Christopher A. Zimmerman: University of California San Francisco
Erica L. Huey: University of California San Francisco
Jamie S. Ahn: University of California San Francisco
Lisa R. Beutler: University of California San Francisco
Chan Lek Tan: University of California San Francisco
Seher Kosar: University of California San Francisco
Ling Bai: University of California San Francisco
Yiming Chen: University of California San Francisco
Timothy V. Corpuz: University of California San Francisco
Linda Madisen: Allen Institute for Brain Science
Hongkui Zeng: Allen Institute for Brain Science
Zachary A. Knight: University of California San Francisco

Nature, 2019, vol. 568, issue 7750, 98-102

Abstract: Abstract Satiation is the process by which eating and drinking reduce appetite. For thirst, oropharyngeal cues have a critical role in driving satiation by reporting to the brain the volume of fluid that has been ingested1–12. By contrast, the mechanisms that relay the osmolarity of ingested fluids remain poorly understood. Here we show that the water and salt content of the gastrointestinal tract are precisely measured and then rapidly communicated to the brain to control drinking behaviour in mice. We demonstrate that this osmosensory signal is necessary and sufficient for satiation during normal drinking, involves the vagus nerve and is transmitted to key forebrain neurons that control thirst and vasopressin secretion. Using microendoscopic imaging, we show that individual neurons compute homeostatic need by integrating this gastrointestinal osmosensory information with oropharyngeal and blood-borne signals. These findings reveal how the fluid homeostasis system monitors the osmolarity of ingested fluids to dynamically control drinking behaviour.

Date: 2019
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DOI: 10.1038/s41586-019-1066-x

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