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 (SuMVglut2 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 SuMVglut2 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 SuMVglut2 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 SuMVglut2 neurones increased sensitivity to sevoflurane or intensified cortical inhibition during sevoflurane anaesthesia. Retrograde and anterograde tracing verified monosynaptic projections from MSVglut2 neurones to SuMVglut2 neurones. The activity of MSVglut2 SuM terminals increased during loss of consciousness but recovered during recovery of consciousness. Optogenetic activation or inhibition of MSVglut2 SuM terminals induced cortical activation or inhibition, respectively, during sevoflurane anaesthesia. CONCLUSIONS Activation of SuMVglut2 neurones or the glutamatergic septo-supramammillary circuit induces behavioural arousal and cortical activation during sevoflurane anaesthesia.

中文翻译：

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小鼠七氟烷麻醉期间上核谷氨酸能神经元对意识状态的调节。


背景 位于下丘脑尾部的颌上核 （SuM） 包括促进觉醒的谷氨酸能神经元。它们在全身麻醉期间调节意识状态的潜在作用仍然未知。方法 我们使用体内纤维光度法、 c-Fos 染色、化学遗传学和光遗传学操作以及脑电图/肌电图来探索谷氨酸能 SuM 神经元 （SuMVglut2 神经元） 在七氟烷麻醉不同阶段的作用。狂犬病介导的逆行和顺行道追踪用于研究从内侧隔膜 （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学操作研究了它们在七氟烷麻醉中的作用。结果 SuMVglut2 神经元的种群活性在意识丧失时降低，但在七氟烷麻醉下意识恢复时增加。它们的活性在抑制期间也降低，但在七氟烷诱导的爆发抑制振荡的爆发期间增加。通过化学遗传学或光遗传学激活 SuMVglut2 神经元会降低对七氟烷的敏感性，在连续稳态麻醉期间诱导行为唤醒和皮质激活，在七氟烷下诱导稳定的爆发抑制振荡。相比之下，SuMVglut2 神经元的化学遗传学或光遗传学抑制增加了对七氟烷的敏感性或加强了七氟烷麻醉期间的皮质抑制。逆行和顺行追踪验证了从 MSVglut2 神经元到 SuMVglut2 神经元的单突触投射。MSVglut2 SuM 末端的活性在意识丧失期间增加，但在意识恢复期间恢复。 在七氟烷麻醉期间，MSVglut2 SuM 末端的光遗传学激活或抑制分别诱导皮质激活或抑制。结论 SuMVglut2 神经元或谷氨酸能隔膜-鼻中支循环的激活在七氟烷麻醉期间诱导行为唤醒和皮质激活。