Yang Li, Fang Fang, Wang Wen-Xu, Xie Yunli, Cang Jing, Li Shi-Bin
From the Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.
Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, Frontiers Center for Brain Science of the Ministry of Education (MOE), Fudan University, Shanghai, China.
Anesth Analg. 2025 Feb 1;140(2):353-365. doi: 10.1213/ANE.0000000000007092. Epub 2024 Jul 15.
Accumulated evidence suggests that brain regions that promote wakefulness also facilitate emergence from general anesthesia (GA). Glutamatergic neurons in the substantia innominata (SI) regulate motivation-related aversive, depressive, and aggressive behaviors relying on heightened arousal. Here, we hypothesize that glutamatergic neurons in the SI are also involved in the regulation of the effects of sevoflurane anesthesia.
With a combination of fiber photometry, chemogenetic and optogenetic tools, behavioral tests, and cortical electroencephalogram recordings, we investigated whether and how SI glutamatergic neurons and their projections to the lateral hypothalamus (LH) regulate sevoflurane anesthesia in adult male mice.
Population activity of glutamatergic neurons in the SI gradually decreased upon sevoflurane-induced loss of consciousness (LOC) and slowly returned as soon as inhalation of sevoflurane discontinued before recovery of consciousness (ROC). Chemogenetic activation of SI glutamatergic neurons dampened the animals' sensitivity to sevoflurane exposure, prolonged induction time (mean ± standard deviation [SD]; 389 ± 67 seconds vs 458 ± 53 seconds; P = .047), and shortened emergence time (305 seconds, 95% confidence interval [CI], 242-369 seconds vs 207 seconds, 95% CI, 135-279 seconds; P = .004), whereas chemogenetic inhibition of these neurons facilitated sevoflurane anesthesia. Furthermore, optogenetic activation of SI glutamatergic neurons and their terminals in LH induced cortical activation and behavioral emergence from different depths of sevoflurane anesthesia.
Our study shows that SI glutamatergic neuronal activity facilitates emergence from sevoflurane anesthesia and provides evidence for the involvement of the SI-LH glutamatergic pathway in the regulation of consciousness during GA.
越来越多的证据表明，促进觉醒的脑区也有助于从全身麻醉（GA）中苏醒。无名质（SI）中的谷氨酸能神经元依靠增强的觉醒调节与动机相关的厌恶、抑郁和攻击行为。在此，我们假设SI中的谷氨酸能神经元也参与七氟醚麻醉效果的调节。
结合纤维光度法、化学遗传学和光遗传学工具、行为测试以及皮质脑电图记录，我们研究了成年雄性小鼠中SI谷氨酸能神经元及其向外侧下丘脑（LH）的投射是否以及如何调节七氟醚麻醉。
七氟醚诱导意识丧失（LOC）时，SI中谷氨酸能神经元的群体活动逐渐降低，在意识恢复（ROC）前停止吸入七氟醚后，其活动迅速缓慢恢复。化学遗传学激活SI谷氨酸能神经元可减弱动物对七氟醚暴露的敏感性，延长诱导时间（平均值±标准差[SD]；389±67秒对458±53秒；P = 0.047），并缩短苏醒时间（305秒，95%置信区间[CI]，242 - 369秒对207秒，95% CI，135 - 279秒；P = 0.004），而对这些神经元的化学遗传学抑制则促进七氟醚麻醉。此外，光遗传学激活SI谷氨酸能神经元及其在LH中的终末可诱导不同深度七氟醚麻醉下的皮质激活和行为苏醒。
我们的研究表明，SI谷氨酸能神经元活动促进七氟醚麻醉后的苏醒，并为SI-LH谷氨酸能通路参与GA期间意识调节提供了证据。
