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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    et al. The sensory circumventricular organs of the mammalian brain. Adv. Anat. Embryol. Cell Biol. 172, 1–122 (2003)

  2. 2.

    Hunger, Thirst, Sex, and Sleep: How the Brain Controls Our Passions (Rowman & Littlefield, 2012)

  3. 3.

    Hypothalamic survival circuits: blueprints for purposive behaviors. Neuron 77, 810–824 (2013)

  4. 4.

    & Salt appetite: a neurohormonal viewpoint. Physiol. Behav. 81, 319–337 (2004)

  5. 5.

    & Central regulation of sodium appetite. Exp. Physiol. 93, 177–209 (2008)

  6. 6.

    , , , & High salt recruits aversive taste pathways. Nature 494, 472–475 (2013)

  7. 7.

    & Thirst. Nutrition 16, 821–826 (2000)

  8. 8.

    & The physiological regulation of thirst and fluid intake. News Physiol. Sci. 19, 1–6 (2004)

  9. 9.

    Angiotensin, thirst, and sodium appetite. Physiol. Rev. 78, 583–686 (1998)

  10. 10.

    , & Drinking caused by the intracranial injection of angiotensin into the rat. J. Physiol. (Lond.) 200, 98–100 (1969)

  11. 11.

    , & Drinking elicited by intracranial microinjection of angiotensin in the cat. Pharmacol. Biochem. Behav. 1, 353–355 (1973)

  12. 12.

    , & Drinking behavior following electrical stimulation of the subfornical organ in the rat. Brain Res. 274, 197–200 (1983)

  13. 13.

    , & Subfornical organ stimulation elicits drinking. Brain Res. Bull. 38, 209–213 (1995)

  14. 14.

    How does the brain sense osmolality? J. Am. Soc. Nephrol. 18, 3056–3059 (2007)

  15. 15.

    , & Osmoreceptors, osmoreception, and osmoregulation. Front. Neuroendocrinol. 15, 231–274 (1994)

  16. 16.

    et al. Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin. Proc. Natl Acad. Sci. USA 102, 17816–17821 (2005)

  17. 17.

    , , , & Millisecond-timescale, genetically targeted optical control of neural activity. Nature Neurosci. 8, 1263–1268 (2005)

  18. 18.

    et al. A resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex. Neuron 71, 995–1013 (2011)

  19. 19.

    et al. Ligand-activated site-specific recombination in mice. Proc. Natl Acad. Sci. USA 93, 10887–10890 (1996)

  20. 20.

    , , & The subfornical organ is the primary locus of sodium-level sensing by Nax sodium channels for the control of salt-intake behavior. J. Neurosci. 24, 9276–9281 (2004)

  21. 21.

    & Central regulation of body-fluid homeostasis. Trends Neurosci. 36, 661–673 (2013)

  22. 22.

    , & Integrative mechanisms and the maintenance of cardiovascular and body fluid homeostasis: the central processing of sensory input derived from the circumventricular organs of the lamina terminalis. Prog. Brain Res. 91, 381–393 (1992)

  23. 23.

    & Sensory circumventricular organs and brain homeostatic pathways. FASEB J. 7, 678–686 (1993)

  24. 24.

    et al. Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons. Neuron 71, 142–154 10.1016/j.neuron.2011.05.028. (2011)

  25. 25.

    , , , & GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain. Nature Neurosci. 7, 1233–1241 (2004)

  26. 26.

    et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nature Neurosci. 13, 133–140 (2010)

  27. 27.

    , , , & Galanin neurons in the medial preoptic area govern parental behaviour. Nature 509, 325–330 (2014)

  28. 28.

    , & AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nature Neurosci. 14, 351–355 (2011)

  29. 29.

    et al. Scalable control of mounting and attack by Esr1+ neurons in the ventromedial hypothalamus. Nature 509, 627–632 (2014)

  30. 30.

    et al. The cells and peripheral representation of sodium taste in mice. Nature 464, 297–301 (2010)

  31. 31.

    , et al. An anatomic gene expression atlas of the adult mouse brain. Nature Neurosci. 12, 356–362 (2009)

  32. 32.

    , et al. Er81 is expressed in a subpopulation of layer 5 neurons in rodent and primate neocortices. Neuroscience 137, 401–412 (2006)

Download references


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


  1. Search for Yuki Oka in:

  2. Search for Mingyu Ye in:

  3. Search for Charles S. Zuker in:


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.

About this article

Publication history






Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Newsletter Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing