Prefrontal Neurophysiological Changes Associated with Subanesthetic Esketamine Accelerating Mice Emergence from Propofol Anesthesia.
Yinying Sun, Bo Li, Yiting Wang, Xuliang Jiang, Su Tang, Jiayi Zhang, Jun Zhang
Brain research bulletin November 22, 2025 DOI: 10.1016/j.brainresbull.2025.111648 via PubMed
Summary
AI-generated from the abstractA low dose of esketamine (2 mg/kg) significantly accelerated awakening from propofol anesthesia in adult C57BL/6J mice. In the prefrontal cortex, 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. It also induced inter-layer phase desynchronization and a premature increase in acetylcholine and 5-hydroxytryptamine levels. The findings suggest that low-dose esketamine facilitates awakening by orchestrating a sequence of neural events in the prefrontal cortex, providing mechanistic insight into paradoxical emergence from anesthesia.
Study at a glance
| Characteristics | Observational study with experimental manipulation Peer reviewed |
|---|---|
| Population | Adult C57BL/6J mice |
| Intervention | Esketamine |
| Dose | 2 mg/kg |
| Topics | Esketamine |
| Keywords | Calcium imaging Neurotransmitter dynamics Paradoxical emergence Prefrontal cortex Esketamine effects esketamine |
| Key finding | Subanesthetic esketamine accelerates awakening from propofol anesthesia in mice by orchestrating a sequence of neural events in the prefrontal cortex, including hastened γ oscillations, altered layer-specific neuronal activation, inter-layer phase desynchronization, and premature increases in acetylcholine and 5-hydroxytryptamine levels. |
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.