Temporally and Spatially Distinct Thirst Satiation Signals

Neuron. 2019 Jul 17;103(2):242-249.e4. doi: 10.1016/j.neuron.2019.04.039. Epub 2019 May 29.


For thirsty animals, fluid intake provides both satiation and pleasure of drinking. How the brain processes these factors is currently unknown. Here, we identified neural circuits underlying thirst satiation and examined their contribution to reward signals. We show that thirst-driving neurons receive temporally distinct satiation signals by liquid-gulping-induced oropharyngeal stimuli and gut osmolality sensing. We demonstrate that individual thirst satiation signals are mediated by anatomically distinct inhibitory neural circuits in the lamina terminalis. Moreover, we used an ultrafast dopamine (DA) sensor to examine whether thirst satiation itself stimulates the reward-related circuits. Interestingly, spontaneous drinking behavior but not thirst drive reduction triggered DA release. Importantly, chemogenetic stimulation of thirst satiation neurons did not activate DA neurons under water-restricted conditions. Together, this study dissected the thirst satiation circuit, the activity of which is functionally separable from reward-related brain activity.

Keywords: appetite; gut-brain axis; homeostasis; reward circuit; satiation; thirst.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism
  • Dopamine / metabolism
  • Drinking / physiology
  • Female
  • GABAergic Neurons / physiology*
  • Glucagon-Like Peptide 1 / metabolism
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Net / physiology*
  • Neural Pathways / physiology*
  • Nitric Oxide Synthase Type I / genetics
  • Nitric Oxide Synthase Type I / metabolism
  • Optogenetics
  • Osmolar Concentration
  • Peptide Fragments / metabolism
  • Physical Stimulation
  • Satiation / physiology*
  • Stomach / innervation*
  • Subfornical Organ / cytology*


  • Luminescent Proteins
  • Peptide Fragments
  • Glucagon-Like Peptide 1
  • Nitric Oxide Synthase Type I
  • glucagon-like peptide 1 (7-37)
  • Calcium
  • Dopamine