Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
CNS Neurosci Ther. 2021 Aug;27(8):941-950. doi: 10.1111/cns.13656. Epub 2021 May 11.
General anesthesia has been widely applied in surgical or nonsurgical medical procedures, but the mechanism behind remains elusive. Because of shared neural circuits of sleep and anesthesia, whether serotonergic system, which is highly implicated in modulation of sleep and wakefulness, regulates general anesthesia as well is worth investigating.
Immunostaining and fiber photometry were used to assess the neuronal activities. Electroencephalography spectra and burst-suppression ratio (BSR) were used to measure anesthetic depth and loss or recovery of righting reflex to indicate the induction or emergence time of general anesthesia. Regulation of serotonergic system was achieved through optogenetic, chemogenetic, or pharmacological methods.
We found that both Fos expression and calcium activity were significantly decreased during general anesthesia. Activation of 5-HT neurons in the dorsal raphe nucleus (DRN) decreased the depth of anesthesia and facilitated the emergence from anesthesia, and inhibition deepened the anesthesia and prolonged the emergence time. Furthermore, agonism or antagonism of 5-HT 1A or 2C receptors mimicked the effect of manipulating DRN serotonergic neurons.
Our results demonstrate that 5-HT neurons in the DRN play a regulative role of general anesthesia, and activation of serotonergic neurons could facilitate emergence from general anesthesia partly through 5-HT 1A and 2C receptors.
全身麻醉已广泛应用于外科或非外科医疗程序，但其背后的机制仍难以捉摸。由于睡眠和麻醉的神经回路共享，涉及调节睡眠和觉醒的 5-羟色胺能系统是否也调节全身麻醉值得研究。
免疫染色和光纤光度法用于评估神经元活动。脑电图谱和爆发抑制比（BSR）用于测量麻醉深度以及翻正反射的丧失或恢复，以指示全身麻醉的诱导或苏醒时间。通过光遗传学、化学遗传学或药理学方法调节 5-羟色胺能系统。
我们发现，全身麻醉期间 Fos 表达和钙活性均显著降低。中缝背核（DRN）5-羟色胺能神经元的激活降低了麻醉深度并促进了麻醉苏醒，而抑制则加深了麻醉并延长了苏醒时间。此外，5-HT1A 或 2C 受体激动剂或拮抗剂模拟了操纵 DRN 5-羟色胺能神经元的作用。
我们的结果表明，DRN 中的 5-羟色胺能神经元在全身麻醉中起调节作用，激活 5-羟色胺能神经元可通过 5-HT1A 和 2C 受体部分促进全身麻醉苏醒。
