Thirst-associated preoptic neurons encode an aversive motivational drive

Science. 2017 Sep 15;357(6356):1149-1155. doi: 10.1126/science.aan6747.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Dehydration / psychology
  • Drinking Behavior*
  • Gene Expression Profiling
  • Mice
  • Motivation / genetics
  • Motivation / physiology*
  • Neurons / physiology
  • Optogenetics
  • Preoptic Area / cytology
  • Preoptic Area / physiology*
  • Single-Cell Analysis
  • TNF Receptor-Associated Factor 2 / genetics
  • Thirst / physiology*


  • TNF Receptor-Associated Factor 2