| First Author | Jang S | Year | 2023 |
| Journal | Exp Mol Med | Volume | 55 |
| Issue | 8 | Pages | 1806-1819 |
| PubMed ID | 37537215 | Mgi Jnum | J:377748 |
| Mgi Id | MGI:7527061 | Doi | 10.1038/s12276-023-01052-7 |
| Citation | Jang S, et al. (2023) Impact of the circadian nuclear receptor REV-ERBalpha in dorsal raphe 5-HT neurons on social interaction behavior, especially social preference. Exp Mol Med 55(8):1806-1819 |
| abstractText | 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-ERBalpha, 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-Erbalpha in dorsal raphe (DR) 5-HT neurons (5-HT(DR)-specific REV-ERBalpha 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-Erbalpha 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-Erbalpha in 5-HT(DR)-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-HT(DR)-specific REV-ERBalpha cKO mice. These results suggest the significance of the circadian regulation of 5-HT levels by REV-ERBalpha in regulating social interaction behaviors. |
