Thirst neurons anticipate the homeostatic consequences of eating and drinking
Open accessAbstract
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.
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Challenges to physiological homeostasis can produce motivated behaviors with strong negative drive states.
“Challenges to physiological homeostasis can also elicit motivated behaviors associated with strong negative “drive” states, such as overheating, thirst, and hunger, designed to appropriately adapt/direct behavior19–21.”
From Neural mechanisms of social homeostasis (2019) · cites this paper as [21]
AgRP and NOS1 neurons show heightened activity during hunger and thirst, their activity elicits an aversive state, and they are essential for driving feeding and drinking behaviors.
“A potentially similar function has been described for arcuate nucleus AgRP neurons and nitric oxide synthase 1 (NOS1) neurons in the subfornical organ (SFO). These neurons show heightened activity during hunger (AgRP) and thirst (NOS1), their activity elicits an aversive state (place avoidance), and they are essential for driving feeding and drinking behaviors, respectively21,227.”
From Neural mechanisms of social homeostasis (2019) · cites this paper as [21]
Fluid restriction generates a robust physiological response including metabolic adaptations that promote fluid conservation and behavioral adaptations that promote fluid consumption.
“Fluid restriction generates a robust physiological response, which includes metabolic adaptations that promote fluid conservation and behavioral adaptations that promote fluid consumption.”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [11]
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References 33 · Cited by 283
Research works printed but not linked: 1
- [15]Kandel ER Principles of neural science 2013 5th McGraw-Hill
- Authors
- Zimmerman, C. A., Lin, Y.-C., Leib, D. E., Guo, L., Huey, E. L., Daly, G. E., Chen, Y., & Knight, Z. A.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Knight, Zachary A.
- ORCID
- Venue
- Nature
- Published
- 2016-08-03
- Volume
- 537
- Issue
- 7622
- Pages
- 680-684
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5161740
- OpenAlex
- W2480035352
- Cited by
- 283
- References
- 33
- Citations by year
- 2026: 17 · 2025: 27 · 2024: 31 · 2023: 23 · 2022: 23 · 2021: 29 · 2020: 30 · 2019: 44 · 2018: 28 · 2017: 25 · 2016: 6
- FWCI
- 21.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Science Foundation
- National Institutes of Health (1dp2dk109533-01)
- National Heart, Lung, and Blood Institute (F31HL131463)
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK089541, DP2-DK109533, P30DK098722, R01DK106399)
- National Institute of Neurological Disorders and Stroke (R01NS094781)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- thirst, subfornical organ, fluid balance, blood composition, dehydration, drinking behavior, calcium dynamics, optogenetics
- MeSH terms
- Animals, Blood, Calcium, Drinking, Eating, Female, Homeostasis, Male, Mouth, Neural Pathways, Neurons, Subfornical Organ, Thirst, Time Factors, Water-Electrolyte Balance, Feedback, Physiological, Mice, Optogenetics
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