Article | Published:

The cellular mechanism for water detection in the mammalian taste system

Nature Neuroscience volume 20, pages 927933 (2017) | Download Citation

Abstract

Initiation of drinking behavior relies on both internal state and peripheral water detection. While central neural circuits regulating thirst have been well studied, it is still unclear how mammals recognize external water. Here we show that acid-sensing taste receptor cells (TRCs) that were previously suggested as the sour taste sensors also mediate taste responses to water. Genetic silencing of these TRCs abolished water-evoked responses in taste nerves. Optogenetic self-stimulation of acid-sensing TRCs in thirsty animals induced robust drinking responses toward light even without water. This behavior was only observed when animals were water-deprived but not under food- or salt-depleted conditions, indicating that the hedonic value of water-evoked responses is highly internal-state dependent. Conversely, thirsty animals lacking functional acid-sensing TRCs showed compromised discrimination between water and nonaqueous fluids. Taken together, this study revealed a function of mammalian acid-sensing TRCs that provide a cue for external water.

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Acknowledgements

We thank B. Ho for help with mouse husbandry. We also thank K. Scott, M. Meister and D.J. Anderson for helpful suggestions. We thank C.S. Zuker (Columbia) and N. Ryba (NIDCR) for generously sharing Pkd2l1-Cre and TRPM5 knockout transgenic animals, H. Matsunami (Duke) for PKD2L1 antibody, S. Lee for technical support and members of the Oka laboratory for comments. This work was supported by Startup funds from the President and Provost of California Institute of Technology and the Biology and Biological Engineering Division of California Institute of Technology. Y.O. is also supported by the Searle Scholars Program, the Mallinckrodt Foundation, the Okawa Foundation, the McKnight Foundation and the Klingenstein-Simons Foundation. Support was provided by DFG WE 2344/9-1 to G.W. Y.O. have disclosed these methods and findings to the Caltech Office of Technology Transfer.

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Affiliations

  1. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.

    • Dhruv Zocchi
    •  & Yuki Oka
  2. Institute for Anatomy, University Hospital, Duisburg-Essen University, Essen, Germany.

    • Gunther Wennemuth

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Contributions

D.Z. and Y.O. conceived the research program. D.Z. and Y.O. designed and carried out the experiments and analyzed data. G.W. maintained and provided CA4 knockout animals. D.Z. analyzed data and, together with Y.O., wrote the paper. Y.O. supervised the entire work.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Yuki Oka.

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DOI

https://doi.org/10.1038/nn.4575

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