• Jia-Yan Li, Shao-Jie Gao, Ran-Ran Li, Wei Wang, Jia Sun, Long-Qing Zhang, Jia-Yi Wu, Dai-Qiang Liu, Pei Zhang, Bo Tian, and Wei Mei.
• Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and Department of Anesthesiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
• Anesthesiology. 2022 May 1; 136 (5): 709-731.

BackgroundThe neural circuitry underlying sevoflurane-induced modulation of consciousness is poorly understood. This study hypothesized that the paraventricular thalamus bed nucleus of the stria terminalis pathway plays an important role in regulating states of consciousness during sevoflurane anesthesia.MethodsRabies virus-based transsynaptic tracing techniques were employed to reveal the neural pathway from the paraventricular thalamus to the bed nucleus of the stria terminalis. This study investigated the role of this pathway in sevoflurane anesthesia induction, maintenance, and emergence using chemogenetic and optogenetic methods combined with cortical electroencephalogram recordings. Both male and female mice were used in this study.ResultsBoth γ-aminobutyric acid-mediated and glutamatergic neurons in the bed nucleus of the stria terminalis receive paraventricular thalamus glutamatergic projections. Chemogenetic inhibition of paraventricular thalamus glutamatergic neurons prolonged the sevoflurane anesthesia emergence time (mean ± SD, hM4D-clozapine N-oxide vs. mCherry-clozapine N-oxide, 281 ± 88 vs. 172 ± 48 s, P < 0.001, n = 24) and decreased the induction time (101 ± 32 vs. 136 ± 34 s, P = 0.002, n = 24), as well as the EC5 0 for the loss or recovery of the righting reflex under sevoflurane anesthesia (mean [95% CI] for the concentration at which 50% of the mice lost their righting reflex, 1.16 [1.12 to 1.20] vs. 1.49 [1.46 to 1.53] vol%, P < 0.001, n = 20; and for the concentration at which 50% of the mice recovered their righting reflex, 0.95 [0.86 to 1.03] vs. 1.34 [1.29 to 1.40] vol%, P < 0.001, n = 20). Similar results were observed during suppression of the paraventricular thalamus bed nucleus-stria terminalis pathway. Optogenetic activation of this pathway produced the opposite effects. Additionally, transient stimulation of this pathway efficiently induced behavioral arousal during continuous steady-state general anesthesia with sevoflurane and reduced the depth of anesthesia during sevoflurane-induced burst suppression.ConclusionsIn mice, axonal projections from the paraventricular thalamic neurons to the bed nucleus of the stria terminalis contribute to regulating states of consciousness during sevoflurane anesthesia.Editor’s PerspectiveCopyright © 2022, the American Society of Anesthesiologists. All Rights Reserved.

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