Letter | Published:

Thirst driving and suppressing signals encoded by distinct neural populations in the brain

Nature volume 520, pages 349352 (16 April 2015) | Download Citation


Thirst is the basic instinct to drink water. Previously, it was shown that neurons in several circumventricular organs of the hypothalamus are activated by thirst-inducing conditions1. Here we identify two distinct, genetically separable neural populations in the subfornical organ that trigger or suppress thirst. We show that optogenetic activation of subfornical organ excitatory neurons, marked by the expression of the transcription factor ETV-1, evokes intense drinking behaviour, and does so even in fully water-satiated animals. The light-induced response is highly specific for water, immediate and strictly locked to the laser stimulus. In contrast, activation of a second population of subfornical organ neurons, marked by expression of the vesicular GABA transporter VGAT, drastically suppresses drinking, even in water-craving thirsty animals. These results reveal an innate brain circuit that can turn an animal’s water-drinking behaviour on and off, and probably functions as a centre for thirst control in the mammalian brain.

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We thank N. Propp for help with mouse husbandry. We also thank H. Fishman for suggestions, Z. Turan, N. Ryba and T. Usdin for technical support, and N. Ryba and members of the Zuker laboratory for comments. We acknowledge B. Lowell and M. Krashes for advice. Y.O. and M.Y. were supported by grants from the National Institute on Drug Abuse and National Institute of Neurological Disorders and Stroke to C.S.Z. C.S.Z. is an investigator of the Howard Hughes Medical Institute.

Author information

Author notes

    • Yuki Oka

    Present address: Division of Biology and Biological Engineering 216-76, California Institute of Technology, Pasadena, California 91125, USA.


  1. Department of Biochemistry and Molecular Biophysics, Columbia College of Physicians and Surgeons, Howard Hughes Medical Institute, Columbia University, New York, New York 10032, USA

    • Yuki Oka
    • , Mingyu Ye
    •  & Charles S. Zuker
  2. Department of Neuroscience, Columbia College of Physicians and Surgeons, Howard Hughes Medical Institute, Columbia University, New York, New York 10032, USA

    • Yuki Oka
    • , Mingyu Ye
    •  & Charles S. Zuker


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Y.O. developed the research program, designed the study, carried out the experiments, and analysed data; M.Y. performed all slice patch clamp recordings; C.S.Z. analysed data, designed experiments and together with Y.O. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Yuki Oka.

Extended data

Supplementary information


  1. 1.

    Stimulation of CamKII-positive Neurons in the SFO Immediately Triggers Drinking Behaviour

    A water-satiated animal expressing ChR2-EYFP under the control of CamKII promoter was photostimulated as shown (“Light”). Upon photostimulation, the animal immediately ceased current activities, searched for water, and started drinking. Note that the animal quickly stopped drinking upon termination of photostimulation.

  2. 2.

    Stimulation of CamKII-positive Neurons in the SFO Triggers Drinking

    Upon photostimulation, mice display robust ChR2-dependent drinking, even if water was presented in an (unfamiliar) object that the animal has never encountered (white bowl).

  3. 3.

    Stimulation of SFO neurons does not induce feeding

    Photostimulation (indicated by “Light”) did not trigger simultaneous feeding responses.

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