A hindbrain dopaminergic neural circuit prevents weight gain by reinforcing food satiation

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 DA(cVTA) 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 DRD1(LPBN) neurons inhibits feeding, whereas genetic deletion of Drd1 within the LPBN causes robust increase in food intake and subsequent weight gain. Furthermore, the DRD1(LPBN) 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.

Automated summary

This study identified a group of dopamine neurons located in the caudal ventral tegmental area that suppress food intake through enhanced satiation response by directly innervating DRD1-expressing neurons in the lateral parabrachial nucleus. Acute inhibition of these neurons before feeding bout termination significantly suppresses satiety and prolongs feeding, while activation of DRD1(LPBN) neurons inhibits feeding. Genetic deletion of Drd1 in LPBN leads to increased food intake and weight gain. Furthermore, DRD1(LPBN) signaling is crucial for methylphenidate-induced hypophagia.