Prefrontal Neurophysiological Changes Associated with Subanesthetic Esketamine Accelerating Mice Emergence from Propofol Anesthesia.
Brain research bulletin – November 22, 2025
Source: PubMed
Summary
A surprising finding reveals that a low dose of esketamine can actually speed up recovery from propofol anesthesia. Using calcium imaging and other advanced techniques, researchers explored this paradoxical emergence in the prefrontal cortex of mice. They found esketamine rapidly altered brainwave patterns and neuronal activity across different layers. Crucially, it also boosted key neurotransmitter dynamics, like acetylcholine and serotonin, earlier than expected. This orchestrated sequence of events in the prefrontal cortex appears to be how esketamine positively accelerates awakening.
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/6J mice were anesthetized with propofol, 0and a low dose of esketamine (2mg/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.