5-HT recruits distinct neurocircuits to inhibit hunger-driven and non-hunger-driven feeding
Yanlin He, Xing Cai, Hailan Liu, Krisitine M. Conde, Pingwen Xu, Yongxiang Li, Chunmei Wang, Meng Yu, Yang He, Hesong Liu, Liang Chen, Tingting Yang, Yongjie Yang, Kaifan Yu, Julia Wang, Rong Zheng, Feng Liu, Zheng Sun, Lora K. Heisler, Qi Wu, Qingchun Tong, Canjun Zhu, Gang Shu, Yong Xu
Abstract
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-HT DRN ) regulate different types of feeding behavior, such as eating to cope with hunger or for pleasure. Here, we observed that activation of 5-HT DRN to hypothalamic arcuate nucleus (5-HT DRN → ARH) projections inhibits food intake driven by hunger via actions at ARH 5-HT 2C and 5-HT 1B receptors, whereas activation of 5-HT DRN to ventral tegmental area (5-HT DRN → VTA) projections inhibits non-hunger-driven feeding via actions at 5-HT 2C receptors. Further, hunger-driven feeding gradually activates ARH-projecting 5-HT DRN neurons via inhibiting their responsiveness to inhibitory GABAergic inputs; non-hunger-driven feeding activates VTA-projecting 5-HT DRN 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.