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Nature. 2019 Apr;568(7750):98-102. doi: 10.1038/s41586-019-1066-x. Epub 2019 Mar 27.

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

Zimmerman CA1,2,3, Huey EL1,2,4, Ahn JS1,2,5, Beutler LR2,6, Tan CL1,2,7, Kosar S1,2, Bai L1,2, Chen Y1,2,3, Corpuz TV1,2, Madisen L8, Zeng H8, Knight ZA9,10,11,12.

Author information

1
Department of Physiology, University of California San Francisco, San Francisco, CA, USA.
2
Kavli Institute for Fundamental Neuroscience, University of California San Francisco, San Francisco, CA, USA.
3
Neuroscience Graduate Program, University of California San Francisco, San Francisco, CA, USA.
4
Graduate Program in Neuroscience, Harvard Medical School, Boston, MA, USA.
5
California Northstate University College of Medicine, Elk Grove, CA, USA.
6
Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
7
Department of Neuroscience, Genentech Inc., South San Francisco, CA, USA.
8
Allen Institute for Brain Science, Seattle, WA, USA.
9
Department of Physiology, University of California San Francisco, San Francisco, CA, USA. zachary.knight@ucsf.edu.
10
Kavli Institute for Fundamental Neuroscience, University of California San Francisco, San Francisco, CA, USA. zachary.knight@ucsf.edu.
11
Neuroscience Graduate Program, University of California San Francisco, San Francisco, CA, USA. zachary.knight@ucsf.edu.
12
Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA, USA. zachary.knight@ucsf.edu.

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.

PMID:
30918408
DOI:
10.1038/s41586-019-1066-x

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