• Yu-Long Wang, Lu Wang, Wei Xu, Miao He, Hui Dong, Huan-Ying Shi, Yong-Quan Chen, and Zhi-Li Huang.
• Department of Anaesthesiology, Yijishan Hospital, Wannan Medical College, Wuhu, China; Department of Pharmacology, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
• Br J Anaesth. 2023 Jun 1; 130 (6): 698708698-708.

BackgroundThe neuronal mechanisms underlying propofol-induced modulation of consciousness are poorly understood. Neuroimaging studies suggest a potential role for non-specific thalamic nuclei in propofol-induced loss of consciousness. We investigated the contribution of the paraventricular thalamus (PVT), a midline thalamic nucleus that has been implicated in arousal control and general anaesthesia with inhaled anaesthetics, to loss and recovery of consciousness during propofol anaesthesia.MethodsPolysomnographic recordings and righting reflex test were used to determine the transitions of loss and recovery of righting reflex, used as a measure of consciousness in mice, during propofol anaesthesia in mice under conditions mimicking clinical propofol administration. PVT neuronal activities were monitored using fibre photometry and regulated using optogenetic and chemogenetic methods.ResultsPopulation activities of PVT glutamatergic neurones began to decrease before propofol-induced loss of consciousness and rapidly increased to a peak at the onset of recovery of consciousness. Chemogenetic inhibition of PVT calretinin-expressing (PVTCR) neurones shortened onset (from 176 [35] to 127 [26] s; P=0.001) and prolonged return (from 1568 [611] to 3126 [1616] s; P=0.002) of righting reflex. Conversely, chemogenetic activation of PVTCR neurones exerted opposite effects. Furthermore, optogenetic silencing of PVTCR neurones accelerated transitions to loss of consciousness (from 205 [35] to 158 [44] s; P=0.027) and slowed transitions to recovery of consciousness (from 230 [78] to 370 [99] s; P=0.041). During a steady period of unconsciousness maintained with continuous propofol infusion, brief optical activation of PVTCR neurones restored cortical activity and arousal with a latency of about 5 s.ConclusionsThe paraventricular thalamus contributes to the control of consciousness transitions in propofol anaesthesia in mice. This provides a potential neuroanatomical target for controlling consciousness to reduce anaesthetic dose requirements and side effects.Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

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