Department of General Zoology and Neurobiology, Ruhr University Bochum, D-44780 Bochum, Germany.
Proc Natl Acad Sci U S A. 2014 Apr 29;111(17):6479-84. doi: 10.1073/pnas.1321576111. Epub 2014 Apr 14.
Serotonin 2c receptors (5-HT2c-Rs) are drug targets for certain mental disorders, including schizophrenia, depression, and anxiety. 5-HT2c-Rs are expressed throughout the brain, making it difficult to link behavioral changes to circuit specific receptor expression. Various 5-HT-Rs, including 5-HT2c-Rs, are found in the dorsal raphe nucleus (DRN); however, the function of 5-HT2c-Rs and their influence on the serotonergic signals mediating mood disorders remain unclear. To investigate the role of 5-HT2c-Rs in the DRN in mice, we developed a melanopsin-based optogenetic probe for activation of Gq signals in cellular domains, where 5-HT2c-Rs are localized. Our results demonstrate that precise temporal control of Gq signals in 5-HT2c-R domains in GABAergic neurons upstream of 5-HT neurons provides negative feedback regulation of serotonergic firing to modulate anxiety-like behavior in mice.
5-羟色胺 2c 受体(5-HT2c-Rs)是某些精神疾病的药物靶点,包括精神分裂症、抑郁症和焦虑症。5-HT2c-Rs 在整个大脑中表达,这使得将行为变化与特定回路的受体表达联系起来变得困难。各种 5-HT-Rs,包括 5-HT2c-Rs,都存在于中缝背核(DRN)中;然而,5-HT2c-Rs 的功能及其对调节情绪障碍的血清素信号的影响仍不清楚。为了研究 5-HT2c-Rs 在 DRN 中的作用,我们开发了一种基于黑视蛋白的光遗传学探针,用于激活细胞区域中的 Gq 信号,5-HT2c-Rs 定位于该区域。我们的结果表明,在 5-HT 神经元上游的 GABA 能神经元中,5-HT2c-R 域内 Gq 信号的精确时间控制为调节 5-HT 神经元的放电提供了负反馈调节,从而调节小鼠的焦虑样行为。