Regulation of states of consciousness by supramammillary nucleus glutamatergic neurones during sevoflurane anaesthesia in mice

IF 9.1 1区医学 Q1 ANESTHESIOLOGY

British journal of anaesthesia Pub Date : 2025-02-01 DOI:10.1016/j.bja.2024.10.023

Jia-Yi Wu , Wei Wang , Xin-Yi Dai , Si He , Fan-He Song , Shao-Jie Gao , Long-Qing Zhang , Dan-Yang Li , Lin Liu , Dai-Qiang Liu , Ya-Qun Zhou , Pei Zhang , Bo Tian , Wei Mei

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引用次数: 0

Abstract

Background

The supramammillary nucleus (SuM), located in the caudal hypothalamus, includes wake-promoting glutamatergic neurones. Their potential role in regulating states of consciousness during general anaesthesia remains unknown.

Methods

We used in vivo fibre photometry, c-Fos staining, chemogenetic and optogenetic manipulations, and electroencephalography/electromyography to explore the roles of glutamatergic SuM neurones (SuM^Vglut2 neurones) at different phases of sevoflurane anaesthesia. Rabies-mediated retrograde and anterograde tract tracing were used to investigate the monosynaptic glutamatergic inputs from the medial septum (MS) to SuM. Their roles in sevoflurane anaesthesia were investigated by in vivo fibre photometry and optogenetic manipulations.

Results

The population activity of SuM^Vglut2 neurones decreased at loss of consciousness but increased during recovery of consciousness under sevoflurane anaesthesia. Their activity also decreased during suppression but increased during bursts in sevoflurane-induced burst-suppression oscillations. Activating SuM^Vglut2 neurones chemogenetically or optogenetically decreased sensitivity to sevoflurane, induced behavioural arousal and cortical activation during continuous steady-state anaesthesia, and stable burst-suppression oscillations under sevoflurane. In contrast, chemogenetic or optogenetic inhibition of SuM^Vglut2 neurones increased sensitivity to sevoflurane or intensified cortical inhibition during sevoflurane anaesthesia. Retrograde and anterograde tracing verified monosynaptic projections from MS^Vglut2 neurones to SuM^Vglut2 neurones. The activity of MS^Vglut2 SuM terminals increased during loss of consciousness but recovered during recovery of consciousness. Optogenetic activation or inhibition of MS^Vglut2 SuM terminals induced cortical activation or inhibition, respectively, during sevoflurane anaesthesia.

Conclusions

Activation of SuM^Vglut2 neurones or the glutamatergic septo-supramammillary circuit induces behavioural arousal and cortical activation during sevoflurane anaesthesia.

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七氟醚麻醉小鼠乳上核谷氨酸能神经元对意识状态的调节。

背景：乳上核（SuM）位于下丘脑尾部，包括促醒的谷氨酸能神经元。它们在全身麻醉时调节意识状态的潜在作用尚不清楚。方法：采用体内纤维光度法、c-Fos染色法、化学发生法、光发生法、脑电图/肌电图等方法探讨谷氨酸能SuM神经元（SuMVglut2神经元）在七氟醚麻醉不同阶段的作用。采用狂犬病介导的逆行和顺行尿道示踪来研究从内侧隔膜（MS）到SuM的单突触谷氨酸能输入。通过体内纤维光度法和光遗传操作研究了它们在七氟醚麻醉中的作用。结果：在七氟醚麻醉下，SuMVglut2神经元群活性在意识丧失时下降，在意识恢复时增加。在七氟醚诱导的爆发抑制振荡中，它们的活性也在抑制期间下降，但在爆发期间增加。化学遗传学或光遗传学激活SuMVglut2神经元降低了对七氟醚的敏感性，在连续稳态麻醉期间诱导了行为唤醒和皮层激活，以及七氟醚下稳定的突发抑制振荡。相比之下，化学发生或光遗传抑制SuMVglut2神经元增加对七氟烷的敏感性或在七氟烷麻醉期间强化皮质抑制。逆行和顺行示踪证实了MSVglut2神经元向SuMVglut2神经元的单突触投射。MSVglut2 SuM末端的活性在意识丧失时升高，在意识恢复时恢复。在七氟醚麻醉期间，MSVglut2 SuM末端的光遗传激活或抑制分别诱导皮层激活或抑制。结论：在七氟醚麻醉期间，SuMVglut2神经元或谷氨酸能间隔-乳头上回路的激活可诱导行为唤醒和皮层激活。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

British journal of anaesthesia 医学-麻醉学

CiteScore

13.50

自引率

7.10%

发文量

488

审稿时长

27 days

期刊介绍： The British Journal of Anaesthesia (BJA) is a prestigious publication that covers a wide range of topics in anaesthesia, critical care medicine, pain medicine, and perioperative medicine. It aims to disseminate high-impact original research, spanning fundamental, translational, and clinical sciences, as well as clinical practice, technology, education, and training. Additionally, the journal features review articles, notable case reports, correspondence, and special articles that appeal to a broader audience. The BJA is proudly associated with The Royal College of Anaesthetists, The College of Anaesthesiologists of Ireland, and The Hong Kong College of Anaesthesiologists. This partnership provides members of these esteemed institutions with access to not only the BJA but also its sister publication, BJA Education. It is essential to note that both journals maintain their editorial independence. Overall, the BJA offers a diverse and comprehensive platform for anaesthetists, critical care physicians, pain specialists, and perioperative medicine practitioners to contribute and stay updated with the latest advancements in their respective fields.