Cited by 390Regulation of Appetite and ObesityNeurotransmitter Receptor Influence on BehaviorNeuroscience of respiration and sleep

Thirst-associated preoptic neurons encode an aversive motivational drive.

Open access
Allen, William E., DeNardo, Laura A., Chen, Michael Z., Liu, Cindy D., Loh, Kyle M., Fenno, Lief E., Ramakrishnan, Charu, Deisseroth, Karl +1 more·2017·Science

Abstract

Water deprivation produces a drive to seek and consume water. How neural activity creates this motivation remains poorly understood. We used activity-dependent genetic labeling to characterize neurons activated by water deprivation in the hypothalamic median preoptic nucleus (MnPO). Single-cell transcriptional profiling revealed that dehydration-activated MnPO neurons consist of a single excitatory cell type. After optogenetic activation of these neurons, mice drank water and performed an operant lever-pressing task for water reward with rates that scaled with stimulation frequency. This stimulation was aversive, and instrumentally pausing stimulation could reinforce lever-pressing. Activity of these neurons gradually decreased over the course of an operant session. Thus, the activity of dehydration-activated MnPO neurons establishes a scalable, persistent, and aversive internal state that dynamically controls thirst-motivated behavior.

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  • Artificial stimulation of neurons in the hypothalamus made mice drink, but mice would work to turn off the stimulation if given a choice, leading the authors to suggest that thirst is essentially aversive.

    “These thirst-study authors found that artificial stimulation of neurons in the hypothalamus made mice drink, but that mice would work to turn off the stimulation if given a choice, thus leading the authors to suggest that thirst is essentially aversive.”

    From Evolving Concepts of Emotion and Motivation (2018) · cites this paper as Allen et al., 2017

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  1. [7]Toates F Motivational Systems Cambridge Univ Press Cambridge 1986

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Authors
Allen, W. E., DeNardo, L. A., Chen, M. Z., Liu, C. D., Loh, K. M., Fenno, L. E., Ramakrishnan, C., Deisseroth, K., & Luo, L.
Affiliations
  • Stanford University (US)
  • Howard Hughes Medical Institute (US)
  • Institute for Stem Cell Biology and Regenerative Medicine (US)
  • Stanford Medicine (US)
Corresponding author
  • Allen, William E.
  • DeNardo, Laura A.
  • Chen, Michael Z.
  • Deisseroth, Karl
  • Luo, Liqun
Venue
Science
Published
2017-09-15
Volume
357
Issue
6356
Pages
1149-1155
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2754841759
Cited by
390
References
52
Citations by year
2026: 41 · 2025: 67 · 2024: 67 · 2023: 39 · 2022: 32 · 2021: 38 · 2020: 43 · 2019: 35 · 2018: 23 · 2017: 3
FWCI
17.33
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Science Foundation (award315464, 1546612)
  • National Institutes of Health (award315463, TR01-MH099642, award340292, R01-NS50835)
  • Howard Hughes Medical Institute (Hughes Collaborative Innovation Award, award315462)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
Keywords
thirst, water deprivation, median preoptic nucleus, hypothalamus, aversive motivation, optogenetic stimulation, internal state
MeSH terms
Animals, Cell Line, Dehydration, Drinking Behavior, Motivation, Neurons, Preoptic Area, Thirst, Gene Expression Profiling, TNF Receptor-Associated Factor 2, Mice, Single-Cell Analysis, Optogenetics

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