A Hindbrain Dopaminergic Neural Circuit Prevents Weight Gain by Reinforcing Food Satiation

Authors

Yong Han
Guobin Xia
Yanlin He
Yang He
Monica Farias
Yong Xu
Qi Wu

Publication Date

5-1-2021

Journal

Science Advances

DOI

10.1126/sciadv.abf8719

PMID

34039606

PMCID

PMC10964976

PubMedCentral® Posted Date

5-26-2021

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Eating, Humans, Rats, Rats, Sprague-Dawley, Rhombencephalon, Satiation, Weight Gain

Abstract

The neural circuitry mechanism that underlies dopaminergic (DA) control of innate feeding behavior is largely uncharacterized. Here, we identified a subpopulation of DA neurons situated in the caudal ventral tegmental area (cVTA) directly innervating DRD1-expressing neurons within the lateral parabrachial nucleus (LPBN). This neural circuit potently suppresses food intake via enhanced satiation response. Notably, this cohort of DAcVTA neurons is activated immediately before the cessation of each feeding bout. Acute inhibition of these DA neurons before bout termination substantially suppresses satiety and prolongs the consummatory feeding. Activation of postsynaptic DRD1LPBN neurons inhibits feeding, whereas genetic deletion of Drd1 within the LPBN causes robust increase in food intake and subsequent weight gain. Furthermore, the DRD1LPBN signaling manifests the central mechanism in methylphenidate-induced hypophagia. In conclusion, our study illuminates a hindbrain DAergic circuit that controls feeding through dynamic regulation in satiety response and meal structure.