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A parabrachial GABAergic-glutamatergic circuit regulates sevoflurane anesthesia via the PB→PVT pathway
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DOI：10.1016/j.trsl.2026.07.004.png)
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Abstract
En 中文
Although general anesthetics have been clinically applied for decades, their neural mechanisms of action remain incompletely understood. Emerging evidence indicates that the parabrachial nucleus (PB) and the paraventricular thalamus (PVT) are critically involved in sevoflurane anesthesia. However, whether the PB→PVT glutamatergic pathway (PBGlu-PVT) and local PB circuit jointly regulate sevoflurane anesthesia remains unknown. By using in vivo fiber photometry recording, our study found that sevoflurane markedly suppressed activity in the PBGlu-PVT pathway, which returned to baseline upon anesthetic withdrawal. Optogenetic activation of PBGlu-PVT prolonged induction time and increased cortical β-power, whereas inhibition shortened induction and delayed emergence. Sevoflurane increased c-Fos expression in PB GABAergic neurons (PBGABA), and enhanced the activity of PBGABA during the anesthesia induction and emergence periods. Chemogenetic activation of PBGABA shortened induction, prolonged emergence, and shifted both LORR and RORR dose-response curves leftward, indicating increased anesthetic sensitivity. During sevoflurane anesthesia, optogenetic activation of PBGABA significantly suppressed PBGlu-PVT terminal activity, preliminarily suggesting the presence of a local inhibitory circuit. GABA levels acting on PB glutamatergic neurons increased during induction and markedly rose after emergence. Both PBGABA and the PBGlu-PVT pathway contribute to the regulation of sevoflurane anesthesia, likely forming a local circuit within the PB. These findings provide mechanistic insight into how sevoflurane modulates excitatory-inhibitory interactions across brainstem-thalamic circuits to regulate transitions of consciousness.
Keywords:
Anesthesia
GABAergic neurons
Glutamatergic neurons
Parabrachial nucleus
Paraventricular thalamus
Sevoflurane
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