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Published April 16, 2015 | Accepted Version + Supplemental Material
Journal Article Open

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


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 conditions. 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.

Additional Information

© 2015 Macmillan Publishers Limited. Received 02 September 2014; Accepted 24 November 2014; Published online 26 January 2015. 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. 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. The authors declare no competing financial interests.

Attached Files

Accepted Version - nihms644831.pdf

Supplemental Material - nature14108-sf1.jpg

Supplemental Material - nature14108-sf2.jpg

Supplemental Material - nature14108-sf3.jpg

Supplemental Material - nature14108-sf4.jpg

Supplemental Material - nature14108-sf5.jpg

Supplemental Material - nature14108-sf6.jpg

Supplemental Material - nature14108-sf7.jpg

Supplemental Material - nature14108-sv1.wmv

Supplemental Material - nature14108-sv2.wmv

Supplemental Material - nature14108-sv3.wmv


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August 20, 2023
March 5, 2024