Work

Prefrontal neurophysiological changes associated with subanesthetic esketamine accelerating mice emergence from propofol anesthesia

Year: 2025

Type: article

Abstract: Recent studies have demonstrated that subanesthetic dose of ketamine or its S-enantiomer, esketamine, can paradoxically accelerate the recovery of consciousness in rodents following general anesthesia. However, the neural mechanisms underlying this "awakening-promoting" effect remain poorly understood. Adult C57BL/6 J mice were anesthetized with propofol, 0and a low dose of esketamine (2 mg/kg) was administered intravenously to assess its awakening effects through behavioral tests. In vivo multichannel electrophysiological recordings, calcium imaging, and two-photon imaging combined with neurotransmitter probes targeting 5-hydroxytryptamine(5-HT) and acetylcholine (ACh) were employed to investigate electrophysiological and neurochemical dynamics in the prefrontal cortex (PFC) during the awakening process. Subanesthetic esketamine significantly accelerated awakening from propofol anesthesia in mice. In the PFC, esketamine hastened the emergence of γ oscillations and triggered earlier activation of neuronal somata and dendrites in layer V, while delaying activation in layer II/III neurons. Additionally, subanesthetic esketamine induced inter-layer phase desynchronization and a premature increase in ACh and 5-HT levels in the PFC during the awakening process. Our findings suggest that low-dose esketamine facilitates mice awakening from propofol anesthesia may by orchestrating a sequence of neural events in the PFC. This study provides novel mechanistic insight into the paradoxical emergence from anesthesia induced by subanesthetic esketamine/ketamine. • Subanesthetic esketamine accelerated emergence from propofol anesthesia in mice; • Subanesthetic esketamine hastened emergence of prefrontal γ-frequency oscillations; • Subanesthetic esketamine induced differential activation of prefrontal layers V and II/II neurons, and inter-layer phase desynchronization; • Subanesthetic esketamine prematurely increased prefrontal ACh and 5-HT levels during the awakening process.

Source: Brain Research Bulletin

DOI: 10.1016/j.brainresbull.2025.111648