Letter | Published:

Thirst neurons anticipate the homeostatic consequences of eating and drinking

Nature volume 537, pages 680684 (29 September 2016) | Download Citation

Abstract

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 tonicity1,2,3. However, most drinking behaviour is regulated too rapidly to be controlled by blood composition directly, and instead seems to anticipate homeostatic imbalances before they arise4,5,6,7,8,9,10,11. 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 meals10,11, the rapid satiation of thirst7,8,9, and the fact that oral cooling is thirst-quenching12,13,14.

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Acknowledgements

C.A.Z. is supported by an NSF Graduate Research Fellowship (grant no. 1144247) and a UCSF Discovery Fellowship. Z.A.K. is a New York Stem Cell Foundation-Robertson Investigator and acknowledges support from the New York Stem Cell Foundation, American Diabetes Association, Rita Allen, McKnight, Sloan, Brain and Behavior Research, Klingenstein, and Program for Breakthrough Biological Research Foundations. This work was supported by an NIH New Innovator Award (DP2-DK109533), R01-DK106399, and R01-NS094781, as well as the UCSF Diabetes and Obesity Centers (U01 DK089541).

Author information

Affiliations

  1. Department of Physiology, University of California, San Francisco, San Francisco, California 94158, USA

    • Christopher A. Zimmerman
    • , Yen-Chu Lin
    • , David E. Leib
    • , Ling Guo
    • , Erica L. Huey
    • , Gwendolyn E. Daly
    • , Yiming Chen
    •  & Zachary A. Knight
  2. Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, California 94158, USA

    • Christopher A. Zimmerman
    • , Yen-Chu Lin
    • , David E. Leib
    • , Ling Guo
    • , Erica L. Huey
    • , Gwendolyn E. Daly
    • , Yiming Chen
    •  & Zachary A. Knight
  3. Neuroscience Graduate Program, University of California, San Francisco, San Francisco, California 94158, USA

    • Christopher A. Zimmerman
    • , David E. Leib
    • , Ling Guo
    • , Yiming Chen
    •  & Zachary A. Knight

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Contributions

C.A.Z. and Z.A.K. conceived the project and designed the experiments. C.A.Z., Y.-C.L., D.E.L., L.G., E.L.H., G.E.D. and Y.C. performed stereotaxic surgery and histology. Y.-C.L. conducted acute slice experiments. C.A.Z. and Y.C. conducted photometry experiments. C.A.Z. conducted optogenetics experiments. C.A.Z. and D.E.L. conducted plasma composition experiments. Y.C. generated the synaptophysin-GCaMP6s construct. C.A.Z., Y.-C.L., Y.C. and Z.A.K. analysed the data. C.A.Z. and Z.A.K. prepared the manuscript with input from all authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Zachary A. Knight.

Reviewer Information Nature thanks M. Krashes, M. McKinley and R. Palmiter for their contribution to the peer review of this work.

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DOI

https://doi.org/10.1038/nature18950

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