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, Chen Liang, Tingting Yang, Yongjie Yang, Kaifan Yu, Julia Wang, Rong Zheng, Feng Liu, Zheng Sun, Lora Heisler, Qi WuQingchun Tong, Canjun Zhu, Gang Shu*, Yong Xu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Number of pages14
JournalMolecular Psychiatry
Early online date21 Jul 2021
DOIs
Publication statusE-pub ahead of print - 21 Jul 2021

Keywords

  • NEURONS REGULATE ENERGY
  • SEROTONIN 2C RECEPTORS
  • FOOD-INTAKE
  • LATERAL HYPOTHALAMUS
  • SYNAPTIC PLASTICITY
  • DOPAMINE NEURONS
  • AGRP NEURONS
  • BODY-WEIGHT
  • BRAIN-STEM
  • CIRCUIT

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