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. 2025 Aug 26:S0007-0912(25)00492-1.
doi: 10.1016/j.bja.2025.07.046. Online ahead of print.

Association between pyramidal neurone spiking in the medial prefrontal cortex and the sedative potency of volatile anaesthetics in mice

Yu Leng  1 , Yaoxin Yang  2 , Qian Li  1 , Yujie Wu  1 , Han Huang  3 , Peng Liang  4 , Donghang Zhang  5 , Cheng Zhou  6 , Hugh C Hemmings Jr  7
Affiliations

Association between pyramidal neurone spiking in the medial prefrontal cortex and the sedative potency of volatile anaesthetics in mice

Yu Leng et al. Br J Anaesth. .

Abstract

Background: The mechanisms underlying volatile anaesthetic-induced unconsciousness remain unclear. Glutamatergic pyramidal neurones and fast-spiking interneurones in cerebral cortex circuits play distinct roles in cortical network dynamics under volatile anaesthesia. We investigated the roles of medial prefrontal cortex (mPFC) pyramidal and fast-spiking interneurones in volatile anaesthetic-induced hypnosis.

Methods: The electrophysiological properties of pyramidal and fast-spiking parvalbumin (PV+) neurones were explored by in vivo multichannel recordings and in vitro patch-clamp electrophysiological recordings. Chemogenetic manipulation was used to test the role of pyramidal neurones in the mPFC in volatile anaesthetic-induced unconsciousness. Nav1.1 knockdown in PV+ neurones was used to regulate activities of pyramidal neurones by PV+-dependent disinhibition and to investigate the role of pyramidal neurone activation in volatile anaesthetic-induced unconsciousness.

Results: Regular-spiking pyramidal neurones and fast-spiking PV+ neurones in the mPFC were identified with distinct spiking properties. Sevoflurane suppressed pyramidal neurone firing frequency and action potential characteristics. Chemogenetic inhibition of pyramidal neurones in the mPFC enhanced the potency of volatile anaesthetics, whereas chemogenetic activation produced the opposite results. Sevoflurane also suppressed the firing of fast-spiking PV+ neurones, with a greater inhibition ratio than that in regular pyramidal neurones; however, sevoflurane did not affect the action potential properties of PV+ neurones. Nav1.1 knockdown in PV+ neurones enhanced sevoflurane-mediated suppression of PV+ neurone activity, leading to pyramidal neurone disinhibition and reduced hypnotic potency.

Conclusion: The excitability of pyramidal neurones in the mPFC primarily determines the sedative potency of volatile anaesthetics in mice.

Keywords: action potential; medial prefrontal cortex; neuronal spiking; parvalbumin neurones; pyramidal neurones; volatile anaesthetics.

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Conflict of interest statement

Declarations of interest HCHJr, serves as the editor-in-chief of the British Journal of Anaesthesia. CZ is a member of the associate editoral board of the British Journal of Anaesthesia. The other authors declare that they have no conflicts of interest.

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