biostudies-literatureDeng HNIDA NIH HHSNIMH NIH HHSNINDS NIH HHSNCI NIH HHS6344-6360.e18https://www.ebi.ac.uk/biostudies/studies/S-EPMC9103523biostudies-literatureUnknown184(26)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 (aIC^Fezf2), which are the pyramidal tract neurons, signal motivational vigor and invigorate need-seeking behavior through projections to the brainstem nucleus tractus solitarii (NTS). aIC^Fezf2 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, aIC^Fezf2 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.CellA genetically defined insula-brainstem circuit selectively controls motivational vigor.PMC9103523R01 MH101214P30 CA045508R01 NS104944R01 MH108924R01 DA050374U19 MH114821Hantman ALi YHuang ZJXiao XLi BYang TRitola KDeng HfalseA genetically defined insula-brainstem circuit selectively controls motivational vigor.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 (aIC^Fezf2), which are the pyramidal tract neurons, signal motivational vigor and invigorate need-seeking behavior through projections to the brainstem nucleus tractus solitarii (NTS). aIC^Fezf2 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, aIC^Fezf2 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.2021-01-01T00:00:00Z2021 Dec2026-05-31T15:53:52.977Z2025-02-19T01:39:23.79ZS-EPMC91035233489057710.1016/j.cell.2021.11.019