Li-Li Duan, Ping Cai, Zhang-Shu Li, Qian-Qian Wang, Lei Zhang, Zhuo-Li Chen, Mai-Jie Zhang, Cheng-Wei Zhang, Zhi-Peng Xu, Li Chen
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引用次数: 0
Abstract
Background: Glutamatergic neurons in the supramammillary nucleus (SuM) have been recently identified as a key node in arousal system, yet their role in regulating general anesthesia remains unclear. The aim of the current study is to study the role of the glutamatergic supramammillary neurons and their projections to the medial septum in mediating the effects of isoflurane anesthesia.
Methods: Fiber photometry recording was used to determine the changes in calcium signals of glutamatergic neurons in the SuM during isoflurane anesthesia. Optogenetic and chemogenetic approaches were employed to manipulate SuM glutamatergic neuron activity, and the effects on cortical activity, behavioral responses, and physiological parameters-including pupil diameter, respiratory rate, and blood pressure-were examined in anesthetized mice. Both male and female mice were used in this study.
Results: The activities of SuM glutamatergic neurons decreased during isoflurane anesthesia and recovered after the emergence. Optogenetic activation of these neurons enhanced cortical activity, decreasing electroencephalogram delta power (mean ± SD, Pre-stimulation vs. Stimulation: 51.35 ± 7.26% vs. 32.08 ± 10.48%, n=8, P=0.002) and burst-suppression ratio (81.82 ± 7.83% vs. 44.53 ± 28.62%, n=8, P=0.002). Furthermore, optogenetic activation altered physiological parameters including enlarged pupil diameter (Pre-stim vs Stim: 1.05 ± 0.08% vs 1.95 ± 0.46%, n=8, P<0.001), increased respiratory rate (0.97 ± 0.07% vs 1.57 ± 0.39%, n=10, P<0.001) and elevated blood pressure, and induced behavioral responses including increased arousal scores and accelerated emergence (Light off vs. Light on, 153.80 ± 40.32 s to 59.88 ± 27.18 s, n=8, P=0.007). Moreover, chemogenetic activation produced similar effects, whereas inhibition led to opposite effects. Finally, optogenetically activating SuM glutamatergic terminals projecting to the medial septum mimicked the effects of activating SuM glutamatergic soma, and increased the activity of medial septum glutamatergic neurons.
Conclusions: Our study identifies glutamatergic neurons of the supramamillary nucleus as key neural substrates regulating isoflurane anesthesia and facilitating emergence through their projecitons to the medial septum.
背景：乳上核谷氨酸能神经元（SuM）最近被发现是觉醒系统的关键节点，但其在全身麻醉中的作用尚不清楚。本研究的目的是研究谷氨酸能乳头上神经元及其向中隔的投射在异氟醚麻醉作用中的作用。方法：采用纤维光度法记录异氟醚麻醉大鼠上颌网膜谷氨酸能神经元钙信号的变化。采用光遗传学和化学遗传学方法来控制SuM谷氨酸能神经元的活动，并在麻醉小鼠中检测对皮质活动、行为反应和生理参数（包括瞳孔直径、呼吸频率和血压）的影响。本研究使用了雄性和雌性小鼠。结果：异氟醚麻醉时，大鼠SuM谷氨酸能神经元活性下降，苏醒后恢复。这些神经元的光遗传激活增强了皮质活动，降低了脑电图δ功率（平均值±SD，预刺激vs刺激：51.35±7.26% vs 32.08±10.48%,n=8， P=0.002）和突发抑制比（81.82±7.83% vs 44.53±28.62%,n=8， P=0.002）。此外，光遗传激活改变了生理参数，包括瞳孔直径增大（刺激前vs刺激前：1.05±0.08% vs 1.95±0.46%,n=8, p）。结论：我们的研究确定了乳状上核的谷氨酸能神经元是调节异氟醚麻醉的关键神经底物，并通过它们向内侧隔膜的投射促进出现。
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.
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