ArticleAnesthesiology2026
Role of Dorsomedial Periaqueductal Gray Glutamatergic Neurons in Promoting Arousal under Multiple General Anesthetics in Mice.
Article in Anesthesiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundGeneral anesthesia may involve shared neural mechanisms. The periaqueductal gray (PAG) plays a critical role in physiologic, instinctive behaviors, as well as sleep-wake regulation. However, the role of the dorsomedial PAG (dmPAG) in regulating the anesthesia-awakening state remains unclear. The study aims to investigate the role of dmPAG glutamatergic neurons in promoting arousal under multiple general anesthetics.
methodsMultiple general anesthetics, including sevoflurane, propofol, ketamine, and dexmedetomidine, were administered to mice of both sexes. Calcium imaging was employed to monitor activity changes in glutamatergic neurons within the dmPAG during anesthesia and arousal. Optogenetic and chemogenetic approaches were used to manipulate neuronal activity and evaluate their effects on anesthesia induction, maintenance, and recovery. Additionally, electroencephalogram recordings were analyzed to assess alterations in spectral power and the burst suppression ratio under anesthesia.
resultsGlutamatergic neuronal activity in the dmPAG was suppressed during sevoflurane anesthesia but increased during wakefulness, with similar patterns observed for all intravenous anesthetics tested. Optogenetic activation of dmPAG glutamatergic neurons significantly prolonged anesthesia induction time (green fluorescent protein [GFP] vs. ChR 2 , 218.8 ± 50.83 s vs. 372.5 ± 40.18 s, P < 0.001) and shortened emergence time (GFP vs. ChR 2 , 230.8 ± 40.44 s vs. 135 ± 19.82 s, P < 0.001) under sevoflurane anesthesia. Electroencephalogram changes characteristic of wakefulness were observed during maintained anesthesia, with the burst suppression ratio decreasing (GFP vs. ChR 2 : 50.08 ± 8.21% vs. 2.15 ± 3.38%, P < 0.001). Chemogenetic activation produced similar effects, while chemogenetic inhibition potentiated the anesthetic effects of all tested anesthetics.
conclusionsThe findings suggest that glutamatergic neurons in the dmPAG may act as a common neural substrate for multiple anesthetic agents, playing a critical role in both the loss and the recovery of consciousness.
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