Postingestive Modulation of Food Seeking Depends on Vagus-Mediated Dopamine Neuron Activity

Neuron. 2020 Jun 3;106(5):778-788.e6. doi: 10.1016/j.neuron.2020.03.009. Epub 2020 Apr 6.

Abstract

Postingestive nutrient sensing can induce food preferences. However, much less is known about the ability of postingestive signals to modulate food-seeking behaviors. Here we report a causal connection between postingestive sucrose sensing and vagus-mediated dopamine neuron activity in the ventral tegmental area (VTA), supporting food seeking. The activity of VTA dopamine neurons increases significantly after administration of intragastric sucrose, and deletion of the NMDA receptor in these neurons, which affects bursting and plasticity, abolishes lever pressing for postingestive sucrose delivery. Furthermore, lesions of the hepatic branch of the vagus nerve significantly impair postingestive-dependent VTA dopamine neuron activity and food seeking, whereas optogenetic stimulation of left vagus nerve neurons significantly increases VTA dopamine neuron activity. These data establish a necessary role of vagus-mediated dopamine neuron activity in postingestive-dependent food seeking, which is independent of taste signaling.

Keywords: Postingestive; Ventral Tegmental Area; dopamine; feeding behavior; food seeking; nutrient sensing; vagus nerve.

Publication types

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

MeSH terms

  • Animals
  • Appetitive Behavior / drug effects*
  • Appetitive Behavior / physiology
  • Conditioning, Operant
  • Dopaminergic Neurons / physiology*
  • Food
  • Mice
  • Mice, Knockout
  • Neuronal Plasticity / physiology
  • Non-Nutritive Sweeteners / administration & dosage
  • Nutritive Sweeteners / administration & dosage*
  • Optogenetics
  • Reinforcement, Psychology
  • Stomach
  • Sucrose / administration & dosage*
  • Sucrose / analogs & derivatives
  • TRPM Cation Channels / genetics
  • Taste
  • Vagus Nerve / physiology*
  • Ventral Tegmental Area / cytology
  • Ventral Tegmental Area / physiology*

Substances

  • Non-Nutritive Sweeteners
  • Nutritive Sweeteners
  • TRPM Cation Channels
  • Trpm5 protein, mouse
  • Sucrose
  • trichlorosucrose