GABAergic neurons in the central amygdala promote emergence from isoflurane anesthesia in mice.

IF 9.1 1区医学 Q1 ANESTHESIOLOGY Anesthesiology Pub Date : 2024-10-28 DOI:10.1097/ALN.0000000000005279

Jin-Sheng Zhang, Wei Yao, Lei Zhang, Zhang-Shu Li, Xia-Ting Gong, Li-Li Duan, Zhi-Xian Huang, Tong Chen, Jin-Chuang Huang, Shu-Xiang Yang, Changxi Yu, Ping Cai, Li Chen

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Abstract

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.

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杏仁核中央的 GABA 能神经元可促进小鼠从异氟醚麻醉中苏醒。

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底。中央杏仁核（CeA）中的GABA能神经元在清醒时具有较高的发射率，并在调节唤醒相关行为中发挥作用。本研究旨在探讨杏仁核中央 GABA 能神经元是否参与异氟醚全身麻醉的调控，并揭示其潜在的神经回路：方法：采用纤维光度记录法测定Vgat-Cre小鼠在异氟烷麻醉过程中CeA GABA能神经元钙信号的变化。化学遗传学和光遗传学方法被用来操纵CeA GABA能神经元的活动，右反射试验被用来确定异氟烷麻醉的诱导和唤醒。皮层脑电图（EEG）记录分别用于评估0.8%和1.4%异氟醚麻醉期间EEG频谱功率和猝发抑制比的变化。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少，并在苏醒过程中恢复。对CeA GABA能神经元的化学激活延迟了异氟烷麻醉的诱导时间（平均值±标度，载体 vs. 氯氮平-氧化物：58.75±5.42 s vs. 67.63±5.01 s；n=8，P=0.0017），缩短了异氟烷麻醉的苏醒时间（385.50±66.26 s vs. 214.60±40.21 s；n=8，P=0.0017）。光遗传激活 CeA GABA 能神经元也产生了类似的效果。此外，光遗传激活降低了脑电图的δ功率（刺激前 vs. 刺激：46.63%±4.40% vs. 34.16%±6.47%；n=8，P=0.0195）和猝发抑制比（83.39%±5.15% vs. 52.60%±12.98%；n=8，P=0.0002）。此外，对基底前脑（BF）中的CeA GABA能神经元末端进行光遗传刺激也促进了大脑皮层的激活，并加速了异氟烷麻醉后的行为唤醒：我们的研究结果表明，CeA GABA能神经元在全身麻醉调节中发挥作用，通过GABA能CeA-BF通路促进行为和大脑皮层从异氟醚麻醉中苏醒。

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来源期刊

Anesthesiology 医学-麻醉学

CiteScore

10.40

自引率

5.70%

发文量

542

审稿时长

3-6 weeks

期刊介绍： With its establishment in 1940, Anesthesiology has emerged as a prominent leader in the field of anesthesiology, encompassing perioperative, critical care, and pain medicine. As the esteemed journal of the American Society of Anesthesiologists, Anesthesiology operates independently with full editorial freedom. Its distinguished Editorial Board, comprising renowned professionals from across the globe, drives the advancement of the specialty by presenting innovative research through immediate open access to select articles and granting free access to all published articles after a six-month period. Furthermore, Anesthesiology actively promotes groundbreaking studies through an influential press release program. The journal's unwavering commitment lies in the dissemination of exemplary work that enhances clinical practice and revolutionizes the practice of medicine within our discipline.