AI Summary
This study investigates the role of astrocytes in promoting consciousness recovery from anesthesia. The research focuses on the paraventricular thalamus (PVT) and its modulation by astrocytes through the Kir4.1 channel. Results suggest that activation of PVT astrocytes enhances recovery, particularly affecting PVTChAT neurons projecting to the prefrontal cortex. This specific PVT->prefrontal cortex projection is implicated in consciousness recovery from sevoflurane anesthesia.
Current anesthetic theory is mostly based on neurons and/or neuronal circuits. A role for astrocytes also has been shown in promoting recovery from volatile anesthesia, while the exact modulatory mechanism and/or the molecular target in astrocytes is still unknown. In this study by animal models in male mice and electrophysiological recordings in vivo and in vitro, we found that activating astrocytes of the paraventricular thalamus (PVT) and/or knocking down PVT astrocytic Kir4.1 promoted the consciousness recovery from sevoflurane anesthesia. Single-cell RNA sequencing of the PVT reveals two distinct cellular subtypes of glutamatergic neurons: PVTGRM and PVTChAT neurons. Patch-clamp recording results proved astrocytic Kir4.1-mediated modulation of sevoflurane on the PVT mainly worked on PVTChAT neurons, which projected mainly to the mPFC. In summary, our findings support the novel conception that there is a specific PVT->prefrontal cortex projection involved in consciousness recovery from sevoflurane anesthesia, which is mediated by the inhibition of sevoflurane on PVT astrocytic Kir4.1 conductance.