한빛사논문
- 조회486
Sangwon Jang1, Inah Park1,2, Mijung Choi1, Jihoon Kim1, Seungeun Yeo3, Sung-Oh Huh4, Ji-Woong Choi5, Cheil Moon1,2, Han Kyoung Choe1, Youngshik Choe3 and Kyungjin Kim1,*
1Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea.
2Convergence Research Advanced Centre for Olfaction, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea.
3Korea Brain Research Institute (KBRI), Daegu 41062, Republic of Korea.
4Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
5Department of Electrical Engineering and Computer Science, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea.
*Corresponding author: correspondence to Kyungjin Kim
Abstract
Social interaction among conspecifics is essential for maintaining adaptive, cooperative, and social behaviors, along with survival among mammals. The 5-hydroxytryptamine (5-HT) neuronal system is an important neurotransmitter system for regulating social behaviors; however, the circadian role of 5-HT in social interaction behaviors is unclear. To investigate whether the circadian nuclear receptor REV-ERBα, a transcriptional repressor of the rate-limiting enzyme tryptophan hydroxylase 2 (Tph2) gene in 5-HT biosynthesis, may affect social interaction behaviors, we generated a conditional knockout (cKO) mouse by targeting Rev-Erbα in dorsal raphe (DR) 5-HT neurons (5-HTDR-specific REV-ERBα cKO) using the CRISPR/Cas9 gene editing system and assayed social behaviors, including social preference and social recognition, with a three-chamber social interaction test at two circadian time (CT) points, i.e., at dawn (CT00) and dusk (CT12). The genetic ablation of Rev-Erbα in DR 5-HTergic neurons caused impaired social interaction behaviors, particularly social preference but not social recognition, with no difference between the two CT points. This deficit of social preference induced by Rev-Erbα in 5-HTDR-specific mice is functionally associated with real-time elevated neuron activity and 5-HT levels at dusk, as determined by fiber-photometry imaging sensors. Moreover, optogenetic inhibition of DR to nucleus accumbens (NAc) 5-HTergic circuit restored the impairment of social preference in 5-HTDR-specific REV-ERBα cKO mice. These results suggest the significance of the circadian regulation of 5-HT levels by REV-ERBα in regulating social interaction behaviors.
논문정보
- Research article
- 2023년 08월 (BRIC 등록일 2023-08-09)
- 국내 연구진
- 생명과학 > 신경생물학
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