Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China.
CNS Neurosci Ther. 2024 Nov;30(11):e70141. doi: 10.1111/cns.70141.
Dorsal raphe nucleus (DRN) serotonergic neurons projecting to the ventral tegmental area (VTA) neural circuit participate in regulating wake-related behaviors; however, the effect and mechanism of which in regulating sleep-wake are poorly understood.
Fiber photometry was used to study DRN serotonergic afferent activity changes in the VTA during sleep-wake processes. Optogenetics and chemogenetics were took advantage to study the effects of DRN serotonergic afferents modulating VTA during sleep-wake. In vivo electrophysiology was employed to investigate how VTA neuronal firings were influenced by upregulation of DRN serotonergic afferents during sleep-wake.
We found that DRN serotonergic afferent activity in the VTA was higher during wake than during NREM and REM sleep. Chemogenetic activation of VTA-projecting DRN serotonergic neurons increased wake, and optogenetic activation of DRN serotonergic terminals in the VTA induced wake during NREM and REM sleep. Furthermore, we found that optogenetic activation of DRN serotonergic terminals in the VTA increased glutamatergic neuronal firing, decreased dopaminergic neuronal firing, but not influenced GABAergic neuronal firing during NREM sleep.
Our findings provide evidence in understanding the role of DRN serotonergic neurons-VTA neural pathway in regulating sleep-wake, in which dynamic VTA dopaminergic, glutamatergic, and GABAergic neuronal firing changes responded to the wake promoting effect of DRN serotonergic afferents.
投射到腹侧被盖区（VTA）的背侧中缝核（DRN）5-羟色胺能神经元参与调节与觉醒相关的行为；然而，其在调节睡眠-觉醒中的作用和机制尚不清楚。
利用光纤光度法研究睡眠-觉醒过程中 DRN 5-羟色胺能传入活动在 VTA 中的变化。利用光遗传学和化学遗传学来研究 DRN 5-羟色胺能传入调节 VTA 在睡眠-觉醒中的作用。利用在体电生理学研究了在睡眠-觉醒期间，上调 DRN 5-羟色胺能传入对 VTA 神经元放电的影响。
我们发现 VTA 中的 DRN 5-羟色胺能传入活动在觉醒时高于非快速眼动（NREM）和快速眼动（REM）睡眠时。化学遗传学激活 VTA 投射的 DRN 5-羟色胺能神经元增加了觉醒，光遗传学激活 VTA 中的 DRN 5-羟色胺能末梢在 NREM 和 REM 睡眠期间诱导觉醒。此外，我们发现 VTA 中的 DRN 5-羟色胺能末梢的光遗传学激活增加了谷氨酸能神经元的放电，降低了多巴胺能神经元的放电，但在 NREM 睡眠期间不影响 GABA 能神经元的放电。
我们的研究结果为理解 DRN 5-羟色胺能神经元-VTA 神经通路在调节睡眠-觉醒中的作用提供了证据，其中 VTA 多巴胺能、谷氨酸能和 GABA 能神经元放电的动态变化对 DRN 5-羟色胺能传入的促觉醒作用作出反应。
