A genetically defined insula-brainstem circuit selectively controls motivational vigor

Cell. 2021 Dec 22;184(26):6344-6360.e18. doi: 10.1016/j.cell.2021.11.019. Epub 2021 Dec 9.

Abstract

The anterior insular cortex (aIC) plays a critical role in cognitive and motivational control of behavior, but the underlying neural mechanism remains elusive. Here, we show that aIC neurons expressing Fezf2 (aICFezf2), which are the pyramidal tract neurons, signal motivational vigor and invigorate need-seeking behavior through projections to the brainstem nucleus tractus solitarii (NTS). aICFezf2 neurons and their postsynaptic NTS neurons acquire anticipatory activity through learning, which encodes the perceived value and the vigor of actions to pursue homeostatic needs. Correspondingly, aIC → NTS circuit activity controls vigor, effort, and striatal dopamine release but only if the action is learned and the outcome is needed. Notably, aICFezf2 neurons do not represent taste or valence. Moreover, aIC → NTS activity neither drives reinforcement nor influences total consumption. These results pinpoint specific functions of aIC → NTS circuit for selectively controlling motivational vigor and suggest that motivation is subserved, in part, by aIC's top-down regulation of dopamine signaling.

Keywords: Fezf2; NTS; alC; anterior insular cortex; dopamine; effort; imaging; motivation; nucleus tractus solitarii; optogenetics; pyramidal tract neurons; vigor.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Animal
  • Brain Stem / physiology*
  • Dopamine / metabolism
  • Female
  • Insular Cortex / physiology*
  • Learning
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motivation*
  • Neural Pathways / physiology*
  • Neurons / physiology
  • Nucleus Accumbens / metabolism
  • Time Factors

Substances

  • Dopamine