title: Thirst neurons anticipate the homeostatic consequences of eating and drinking.
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 tonicity. However, most drinking behaviour is regulated too rapidly to be controlled by blood composition directly, and instead seems to anticipate homeostatic imbalances before they arise. 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 meals, the rapid satiation of thirst, and the fact that oral cooling is thirst-quenching.
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, California 94158, USA.|Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, California 94158, USA.|Neuroscience Graduate Program, University of California, San Francisco, San Francisco, California 94158, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Zimmerman
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, California 94158, USA.|Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, California 94158, USA.
authors.forename: Yen-Chu
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, California 94158, USA.|Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, California 94158, USA.|Neuroscience Graduate Program, University of California, San Francisco, San Francisco, California 94158, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Leib
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, California 94158, USA.|Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, California 94158, USA.|Neuroscience Graduate Program, University of California, San Francisco, San Francisco, California 94158, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, California 94158, USA.|Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, California 94158, USA.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Huey
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, California 94158, USA.|Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, California 94158, USA.
authors.forename: Gwendolyn E
authors.initials: GE
authors.lastname: Daly
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, California 94158, USA.|Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, California 94158, USA.|Neuroscience Graduate Program, University of California, San Francisco, San Francisco, California 94158, USA.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, California 94158, USA.|Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, California 94158, USA.|Neuroscience Graduate Program, University of California, San Francisco, San Francisco, California 94158, USA.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Knight
mesh_terms: D000818:Animals; D001769:Blood; D002118:Calcium / Q000378:metabolism; D004326:Drinking / Q000502:physiology*; D004435:Eating / Q000502:physiology*; D025461:Feedback, Physiological; D005260:Female; D006706:Homeostasis; D008297:Male; D051379:Mice; D009055:Mouth / Q000294:innervation / Q000502:physiology; D009434:Neural Pathways; D009474:Neurons / Q000502:physiology*; D062308:Optogenetics; D013356:Subfornical Organ / Q000166:cytology* / Q000502:physiology; D013894:Thirst / Q000502:physiology*; D013997:Time Factors; D014882:Water-Electrolyte Balance / Q000502:physiology*
chemical_list: D002118:Calcium