Activity of the sodium leak channel maintains the excitability of paraventricular thalamus glutamatergic neurons to resist anesthetic effects of sevoflurane in mice

Yujie Wu; Donghang Zhang; Jin Liu; Jingyao Jiang; Keyu Xie; Lin Wu; Yu Leng; Peng Liang; Tao Zhu; Cheng Zhou

doi:10.1097/ALN.0000000000005015

Activity of the sodium leak channel maintains the excitability of paraventricular thalamus glutamatergic neurons to resist anesthetic effects of sevoflurane in mice

Anesthesiology. 2024 Apr 16. doi: 10.1097/ALN.0000000000005015. Online ahead of print.

Authors

Yujie Wu^{1

2}, Donghang Zhang^{1

2}, Jin Liu^{1

2}, Jingyao Jiang^{1

2}, Keyu Xie^{1

2}, Lin Wu^{1

2}, Yu Leng^{1

2}, Peng Liang¹, Tao Zhu¹, Cheng Zhou²

Affiliations

¹ Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, China.
² Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, China.

PMID: 38625708
DOI: 10.1097/ALN.0000000000005015

Abstract

Background: Stimulation of the paraventricular thalamus has been found to enhance anesthesia recovery; however, the underlying molecular mechanism by which general anesthetics modulate paraventricular thalamus is unclear. Here, we aimed to test the hypothesis that the sodium leak channel (NALCN) maintains neuronal activity in paraventricular thalamus to resist anesthetic effects of sevoflurane in mice.

Method: Chemogenetic and optogenetic manipulations, in vivo multiple-channel recordings, and electroencephalogram recordings were used to investigate the role of paraventricular thalamus neuronal activity in sevoflurane anesthesia. Virus-mediated knockdown and/or overexpression was applied to determine how sodium leak channel influenced excitability of paraventricular thalamus glutamatergic neurons under sevoflurane. Viral tracers and local field potentials were used to explore the downstream pathway.

Results: Single neuronal spikes in the paraventricular thalamus were suppressed by sevoflurane anesthesia and recovered during emergence. Optogenetic activation of paraventricular thalamus glutamatergic neurons shortened the emergence period from sevoflurane anesthesia, while chemogenetic inhibition had the opposite effect. Knockdown of sodium leak channel in paraventricular thalamus delayed the emergence from sevoflurane anesthesia (recovery time: from 24 ± 14 to 64 ± 19 s, P < 0.001; concentration for recovery of the righting reflex: from 1.13% ± 0.10% to 0.97% ± 0.13%, P < 0.01). As expected, the overexpression of sodium leak channel in the paraventricular thalamus produced the opposite effects. At the circuit level, knockdown of sodium leak channel in the paraventricular thalamus decreased the neuronal activity of the nucleus accumbens, as indicated by the local field potential and decreased single neuronal spikes in the nucleus accumbens. Additionally, the effects of sodium leak channel knockdown in the paraventricular thalamus on sevoflurane actions were reversed by optical stimulation of the nucleus accumbens.

Conclusions: Activity of sodium leak channel maintains the excitability of paraventricular thalamus glutamatergic neurons to resist the anesthetic effects of sevoflurane in mice.