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Thirst-associated preoptic neurons encode an aversive motivational drive.
Open accessAbstract
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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“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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Metadata
- 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
- ORCID
- Venue
- Science
- Published
- 2017-09-15
- Volume
- 357
- Issue
- 6356
- Pages
- 1149-1155
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC5723384
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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