5-HT Recruits Distinct Neurocircuits To Inhibit Hunger-Driven and Non-Hunger-Driven Feeding

Authors

Yanlin He
Xing Cai
Hailan Liu
Krisitine M Conde
Pingwen Xu
Yongxiang Li
Chunmei Wang
Meng Yu
Yang He
Hesong Liu
Chen Liang
Tingting Yang
Yongjie Yang
Kaifan Yu
Julia Wang
Rong Zheng
Feng Liu
Zheng Sun
Lora Heisler
Qi Wu
Qingchun Tong
Canjun Zhu
Gang Shu
Yong Xu

Publication Date

12-1-2021

Journal

Molecular Psychiatry

DOI

10.1038/s41380-021-01220-z

PMID

34290371

PMCID

34290371

PubMedCentral® Posted Date

12-26-2021

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Dorsal Raphe Nucleus, Hunger, Neurons, Serotonin, Ventral Tegmental Area

Abstract

Obesity is primarily a consequence of consuming calories beyond energetic requirements, but underpinning drivers have not been fully defined. 5-Hydroxytryptamine (5-HT) neurons in the dorsal Raphe nucleus (5-HTDRN) regulate different types of feeding behavior, such as eating to cope with hunger or for pleasure. Here, we observed that activation of 5-HTDRN to hypothalamic arcuate nucleus (5-HTDRN → ARH) projections inhibits food intake driven by hunger via actions at ARH 5-HT2C and 5-HT1B receptors, whereas activation of 5-HTDRN to ventral tegmental area (5-HTDRN → VTA) projections inhibits non-hunger-driven feeding via actions at 5-HT2C receptors. Further, hunger-driven feeding gradually activates ARH-projecting 5-HTDRN neurons via inhibiting their responsiveness to inhibitory GABAergic inputs; non-hunger-driven feeding activates VTA-projecting 5-HTDRN neurons through reducing a potassium outward current. Thus, our results support a model whereby parallel circuits modulate feeding behavior either in response to hunger or to hunger-independent cues.