Department of Anaesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Anaesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Br J Anaesth. 2024 Feb;132(2):320-333. doi: 10.1016/j.bja.2023.08.033. Epub 2023 Nov 11.
The neural mechanisms underlying sevoflurane-induced loss of consciousness and recovery of consciousness after anaesthesia remain unknown. We investigated whether glutamatergic pedunculopontine tegmental nucleus (PPT) neurones are involved in the regulation of states of consciousness under sevoflurane anaesthesia.
In vivo fibre photometry combined with electroencephalography (EEG)/electromyography recording was used to record changes in the activity of glutamatergic PPT neurones under sevoflurane anaesthesia. Chemogenetic and cortical EEG recordings were used to explore their roles in the induction of and emergence from sevoflurane anaesthesia. Optogenetic methods combined with EEG recordings were used to explore the roles of glutamatergic PPT neurones and of the PPT-ventral tegmental area pathway in maintenance of anaesthesia.
The population activity of glutamatergic PPT neurones was reduced before sevoflurane-induced loss of righting reflex and gradually recovered after return of righting reflex. Chemogenetic inhibition of glutamatergic PPT neurones accelerated induction of anaesthesia (hM4Di-CNO vs mCherry-CNO, 76 [17] vs 121 [27] s, P<0.0001) and delayed emergence from sevoflurane anaesthesia (278 [98] vs 145 [53] s, P<0.0001) but increased sevoflurane sensitivity. Optogenetic stimulation of glutamatergic PPT neurons or of the PPT-ventral tegmental area pathway promoted cortical activation and behavioural emergence during steady-state sevoflurane anaesthesia, reduced the depth of anaesthesia, and caused cortical arousal during sevoflurane-induced EEG burst suppression.
Glutamatergic PPT neurones regulate induction and emergence of sevoflurane anaesthesia.
七氟醚诱导麻醉意识丧失和恢复意识的神经机制尚不清楚。我们研究了谷氨酸能脑桥被盖核（PPT）神经元是否参与七氟醚麻醉下意识状态的调节。
在体光纤光度法结合脑电图（EEG）/肌电图记录，记录七氟醚麻醉下谷氨酸能 PPT 神经元活性的变化。化学遗传和皮质 EEG 记录用于探索它们在七氟醚麻醉诱导和苏醒中的作用。光遗传方法结合 EEG 记录用于探索谷氨酸能 PPT 神经元和 PPT-腹侧被盖区通路在维持麻醉中的作用。
七氟醚诱导翻正反射丧失前，谷氨酸能 PPT 神经元群体活动减少，翻正反射恢复后逐渐恢复。化学遗传抑制谷氨酸能 PPT 神经元加速麻醉诱导（hM4Di-CNO 与 mCherry-CNO，76 [17]与 121 [27]秒，P<0.0001），延迟七氟醚麻醉苏醒（278 [98]与 145 [53]秒，P<0.0001），但增加七氟醚敏感性。谷氨酸能 PPT 神经元或 PPT-腹侧被盖区通路的光遗传刺激促进了稳定状态七氟醚麻醉期间皮质激活和行为苏醒，降低了麻醉深度，并在七氟醚诱导的 EEG 爆发抑制期间引起皮质觉醒。
谷氨酸能 PPT 神经元调节七氟醚麻醉的诱导和苏醒。
