Wu Jia-Yi, Wang Wei, Dai Xin-Yi, He Si, Song Fan-He, Gao Shao-Jie, Zhang Long-Qing, Li Dan-Yang, Liu Lin, Liu Dai-Qiang, Zhou Ya-Qun, Zhang Pei, Tian Bo, Mei Wei
Department of Anaesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anaesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anaesthesia, Tongji Hospital, China.
Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Br J Anaesth. 2025 Feb;134(2):425-440. doi: 10.1016/j.bja.2024.10.023. Epub 2024 Dec 6.
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.
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 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.
The population activity of SuM 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 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 neurones increased sensitivity to sevoflurane or intensified cortical inhibition during sevoflurane anaesthesia. Retrograde and anterograde tracing verified monosynaptic projections from MS neurones to SuM neurones. The activity of MS SuM terminals increased during loss of consciousness but recovered during recovery of consciousness. Optogenetic activation or inhibition of MS SuM terminals induced cortical activation or inhibition, respectively, during sevoflurane anaesthesia.
Activation of SuM neurones or the glutamatergic septo-supramammillary circuit induces behavioural arousal and cortical activation during sevoflurane anaesthesia.
乳头体上核（SuM）位于下丘脑尾部，包含促进觉醒的谷氨酸能神经元。其在全身麻醉期间调节意识状态的潜在作用尚不清楚。
我们使用体内光纤光度法、c-Fos染色、化学遗传学和光遗传学操作以及脑电图/肌电图来探究谷氨酸能SuM神经元（SuM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束路示踪法研究内侧隔区（MS）到SuM的单突触谷氨酸能输入。通过体内光纤光度法和光遗传学操作研究它们在七氟醚麻醉中的作用。
在七氟醚麻醉下，意识消失时SuM神经元的群体活动降低，但意识恢复期间增加。在七氟醚诱导的爆发抑制振荡中，其活动在抑制期降低，但在爆发期增加。化学遗传学或光遗传学激活SuM神经元会降低对七氟醚的敏感性，在持续稳态麻醉期间诱导行为觉醒和皮层激活，并在七氟醚作用下产生稳定的爆发抑制振荡。相反，化学遗传学或光遗传学抑制SuM神经元会增加对七氟醚的敏感性或在七氟醚麻醉期间增强皮层抑制。逆行和顺行示踪证实了从MS神经元到SuM神经元的单突触投射。意识消失期间，MS-SuM终末的活动增加，但意识恢复期间恢复。在七氟醚麻醉期间，光遗传学激活或抑制MS-SuM终末分别诱导皮层激活或抑制。
激活SuM神经元或谷氨酸能隔区-乳头体上核回路可在七氟醚麻醉期间诱导行为觉醒和皮层激活。
