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

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Thirst-associated preoptic neurons encode an aversive motivational drive.

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Allen, William E., DeNardo, Laura A., Chen, Michael Z., Liu, Cindy D., Loh, Kyle M., Fenno, Lief E., Ramakrishnan, Charu, Deisseroth, Karl, Luo, Liqun·2017·Science

DOI 10.1126/science.aan6747PMC PMC5723384

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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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Additional file 1 of CPT1A in AgRP neurons is required for sex-dependent regulation of feeding and thirst
Zagmutt, S., Mera, P., González‐García, I., Ibeas, K., Romero, M. D. M., Obri, A., Martin, B., Esteve‐Codina, A., Soler‐Vázquez, M. C., Bastías-Pérez, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26577719
Additional file 5 of CPT1A in AgRP neurons is required for sex-dependent regulation of feeding and thirst
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Additional file 7 of CPT1A in AgRP neurons is required for sex-dependent regulation of feeding and thirst
Zagmutt, S., Mera, P., González‐García, I., Ibeas, K., Romero, M. D. M., Obri, A., Martin, B., Esteve‐Codina, A., Soler‐Vázquez, M. C., Bastías-Pérez, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26577737
Additional file 3 of CPT1A in AgRP neurons is required for sex-dependent regulation of feeding and thirst
Zagmutt, S., Mera, P., González‐García, I., Ibeas, K., Romero, M. D. M., Obri, A., Martin, B., Esteve‐Codina, A., Soler‐Vázquez, M. C., Bastías-Pérez, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26577725
Additional file 2 of CPT1A in AgRP neurons is required for sex-dependent regulation of feeding and thirst
Zagmutt, S., Mera, P., González‐García, I., Ibeas, K., Romero, M. D. M., Obri, A., Martin, B., Esteve‐Codina, A., Soler‐Vázquez, M. C., Bastías-Pérez, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26577722
Additional file 4 of CPT1A in AgRP neurons is required for sex-dependent regulation of feeding and thirst
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Using light to control brain cells – neuroscientist Karl Deisseroth explains how he made his Nobel-winning discovery
Deisseroth, K. A. (2026) · doi:10.64628/aai.cvt5vsvx6

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: Allen, William E.
DeNardo, Laura A.
Chen, Michael Z.
Liu, Cindy D.
Loh, Kyle M.
Fenno, Lief E.
Ramakrishnan, Charu
Deisseroth, Karl
Luo, Liqun
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2017-09-15
Volume: 357
Issue: 6356
Pages: 1149-1155
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.aan6747
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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Thirst-associated preoptic neurons encode an aversive motivational drive.

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