Neurons for hunger and thirst transmit a negative-valence teaching signal

Nature. 2015 May 14;521(7551):180-185. doi: 10.1038/nature14416. Epub 2015 Apr 27.


Homeostasis is a biological principle for regulation of essential physiological parameters within a set range. Behavioural responses due to deviation from homeostasis are critical for survival, but motivational processes engaged by physiological need states are incompletely understood. We examined motivational characteristics of two separate neuron populations that regulate energy and fluid homeostasis by using cell-type-specific activity manipulations in mice. We found that starvation-sensitive AGRP neurons exhibit properties consistent with a negative-valence teaching signal. Mice avoided activation of AGRP neurons, indicating that AGRP neuron activity has negative valence. AGRP neuron inhibition conditioned preference for flavours and places. Correspondingly, deep-brain calcium imaging revealed that AGRP neuron activity rapidly reduced in response to food-related cues. Complementary experiments activating thirst-promoting neurons also conditioned avoidance. Therefore, these need-sensing neurons condition preference for environmental cues associated with nutrient or water ingestion, which is learned through reduction of negative-valence signals during restoration of homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti-Related Protein / metabolism
  • Animals
  • Cues
  • Dehydration
  • Drinking / physiology*
  • Eating / physiology*
  • Food
  • Food Preferences
  • Homeostasis
  • Hunger / physiology*
  • Hypothalamus / metabolism
  • Male
  • Mice
  • Models, Animal
  • Neurons / metabolism*
  • Starvation
  • Thirst / physiology*


  • Agouti-Related Protein