Journal
SCIENCE
Volume 357, Issue 6356, Pages 1149-1155Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aan6747
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Funding
- Fannie & John Hertz Foundation Fellowship
- NSF Graduate Research Fellowship
- Defense Advanced Research Projects Agency Neuro-FAST program
- NOMIS Foundation
- Tarlton Foundation
- Wiegers Family Fund
- Nancy and James Grosfeld Foundation
- H. L. Snyder Medical Foundation
- Samuel and Betsy Reeves Fund
- Hughes Collaborative Innovation Award
- National Institute of Mental Health
- NSF
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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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