BACKGROUND Recent evidence indicates that general anesthesia and sleep-wake behavior share some overlapping neural substrates. GABAergic neurons in the central amygdala (CeA) have a high firing rate during wakefulness and play a role in regulating arousal-related behaviors. The objective of this study is to investigate whether CeA GABAergic neurons participate in the regulation of isoflurane general anesthesia and uncover the underlying neural circuitry. METHODS Fiber photometry recording was used to determine the changes in calcium signals of CeA GABAergic neurons during isoflurane anesthesia in Vgat-Cre mice. Chemogenetic and optogenetic approaches were used to manipulate the activity of CeA GABAergic neurons, and a righting reflex test was used to determine the induction and emergence from isoflurane anesthesia. Cortical electroencephalogram (EEG) recording was used to assess the changes in EEG spectral power and burst-suppression ratio during 0.8% and 1.4% isoflurane anesthesia, respectively. Both male and female mice were used in this study. RESULTS The calcium signals of CeA GABAergic neurons decreased during the induction of isoflurane anesthesia and was restored during the emergence. Chemogenetic activation of CeA GABAergic neurons delayed induction time (mean ± SD, vehicle vs. clozapine-N-oxide: 58.75±5.42 s vs. 67.63±5.01 s; n=8, P=0.0017) and shortened emergence time (385.50±66.26 s vs. 214.60±40.21 s; n=8, P=0.0017) from isoflurane anesthesia. Optogenetic activation of CeA GABAergic neurons produced a similar effect. Furthermore, optogenetic activation decreased EEG delta power (Pre-stim vs. Stim: 46.63%±4.40% vs. 34.16%±6.47%; n=8, P=0.0195) and burst-suppression ratio (83.39%±5.15% vs. 52.60%±12.98%; n=8, P=0.0002). Moreover, optogenetic stimulation of terminals of CeA GABAergic neurons in the basal forebrain (BF) also promoted cortical activation and accelerated behavioral emergence from isoflurane anesthesia. CONCLUSIONS Our results suggest that CeA GABAergic neurons play a role in general anesthesia regulation, which facilitates behavioral and cortical emergence from isoflurane anesthesia through the GABAergic CeA-BF pathway.

中文翻译：

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中央杏仁核中的 GABA 能神经元促进小鼠从异氟醚麻醉中出现。


背景 最近的证据表明，全身麻醉和睡眠-觉醒行为有一些重叠的神经基质。中枢杏仁核 （CeA） 中的 GABA 能神经元在清醒时具有高放电率，并在调节觉醒相关行为中发挥作用。本研究的目的是调查 CeA GABA 能神经元是否参与异氟醚全身麻醉的调节并揭示潜在的神经回路。方法 采用纤维光度法记录测定 Vgat-Cre 小鼠异氟醚麻醉期间 CeA GABA 能神经元钙信号的变化。化学遗传学和光遗传学方法用于操纵 CeA GABA 能神经元的活性，并使用扶正反射试验来确定异氟醚麻醉的诱导和苏醒。皮质脑电图 （EEG） 记录分别用于评估 0.8% 和 1.4% 异氟醚麻醉期间 EEG 频谱功率和突发抑制率的变化。本研究使用了雄性和雌性小鼠。结果 CeA GABA 能神经元的钙信号在异氟醚麻醉诱导过程中减弱，在出现过程中恢复。CeA GABA 能神经元的化学遗传学激活延迟了异氟醚麻醉的诱导时间 （平均 ± SD，载体 vs. 氯氮平-N-氧化物：58.75±5.42 s vs. 67.63±5.01 s;n=8，P = 0.0017）和缩短的出现时间 （385.50±66.26 s vs. 214.60±40.21 s;n=8，P = 0.0017）。CeA GABA 能神经元的光遗传学激活产生了类似的效果。此外，光遗传学激活降低了脑电图增量功率 （Pre-stim vs. Stim： 46.63%±4.40% vs. 34.16%±6.47%;n=8，P = 0.0195）和爆发抑制率 （83.39%±5.15% vs. 52.60%±12.98%;n=8，P = 0.0002）。 此外，基底前脑 （BF） 中 CeA GABA 能神经元末端的光遗传学刺激也促进了皮质活化并加速了异氟醚麻醉的行为出现。结论 我们的结果表明，CeA GABA 能神经元在全身麻醉调节中发挥作用，通过 GABA 能 CeA-BF 通路促进异氟醚麻醉的行为和皮质出现。