Activation of glutamatergic neurones in the pedunculopontine tegmental nucleus promotes cortical activation and behavioural emergence from sevoflurane-induced unconsciousness in mice

Jiayan Li; Rong Hu; Wulin Tan; Jing Li; Wenqi Huang; Zhongxing Wang

doi:10.1016/j.bja.2023.08.033

Activation of glutamatergic neurones in the pedunculopontine tegmental nucleus promotes cortical activation and behavioural emergence from sevoflurane-induced unconsciousness in mice

Br J Anaesth. 2024 Feb;132(2):320-333. doi: 10.1016/j.bja.2023.08.033. Epub 2023 Nov 11.

Authors

Jiayan Li¹, Rong Hu¹, Wulin Tan¹, Jing Li¹, Wenqi Huang², Zhongxing Wang³

Affiliations

¹ Department of Anaesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
² Department of Anaesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: huangwq@mail.sysu.edu.cn.
³ Department of Anaesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: wzhxing@mail.sysu.edu.cn.

PMID: 37953203
DOI: 10.1016/j.bja.2023.08.033

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: Glutamatergic PPT neurones regulate induction and emergence of sevoflurane anaesthesia.

Keywords: consciousness; glutamatergic neurones; mechanism of anaesthesia; pedunculopontine tegmental nucleus; sevoflurane; ventral tegmental area.

MeSH terms

Animals
Electroencephalography
Mice
Neurons
Pedunculopontine Tegmental Nucleus*
Sevoflurane* / pharmacology
Unconsciousness* / chemically induced

Substances

Sevoflurane