5-HT Neurons Integrate GABA and Dopamine Inputs to Regulate Meal Initiation.

Autor: Conde KM; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Wong H; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Fang S; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Li Y; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Yu M; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Deng Y; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Liu Q; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Fang X; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Wang M; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Shi Y; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Ginnard OZ; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Yang Y; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Tu L; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Liu H; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Liu H; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Yin N; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Bean JC; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Han J; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Burt ME; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Jossy SV; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Yang Y; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Tong Q; Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA., Arenkiel BR; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Wang C; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., He Y; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Xu Y; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Apr 29. Date of Electronic Publication: 2024 Apr 29.
DOI: 10.1101/2024.04.26.591360
Abstrakt: Obesity is a growing global health epidemic with limited effective therapeutics. Serotonin (5-HT) is one major neurotransmitter which remains an excellent target for new weight-loss therapies, but there remains a gap in knowledge on the mechanisms involved in 5-HT produced in the dorsal Raphe nucleus (DRN) and its involvement in meal initiation. Using a closed-loop optogenetic feeding paradigm, we showed that the 5-HT DRN →arcuate nucleus (ARH) circuit plays an important role in regulating meal initiation. Incorporating electrophysiology and ChannelRhodopsin-2-Assisted Circuit Mapping, we demonstrated that 5-HT DRN neurons receive inhibitory input partially from GABAergic neurons in the DRN, and the 5-HT response to GABAergic inputs can be enhanced by hunger. Additionally, deletion of the GABA A receptor subunit in 5-HT neurons inhibits meal initiation with no effect on the satiation process. Finally, we identified the instrumental role of dopaminergic inputs via dopamine receptor D2 in 5-HT DRN neurons in enhancing the response to GABA-induced feeding. Thus, our results indicate that 5-HT DRN neurons are inhibited by synergistic inhibitory actions of GABA and dopamine, which allows for the initiation of a meal.
Competing Interests: DECLARATION OF INTERESTS: The authors declare no competing interests.
Databáze: MEDLINE
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