Somatostatin-expressing Neurons in the Medial Prefrontal Cortex Promote Sevoflurane Anesthesia in Mice

作者：Aichen Tang, Mao Xu, Xizu Chen, Juan Liu, Jiamin Wang, Ying Wang, Shuang Cai, Yue Shu, Danxu Zheng, Tian Yu, Yuan Wang, Tianyuan Luo, Shouyang Yu · 发表于：Anesthesiology · 年份：2025 · DOI：10.1097/aln.0000000000005394 · 被引用次数：6 · 研究领域：Anesthesia and Neurotoxicity Research、Anesthesia and Sedative Agents、Neuroscience and Neuropharmacology Research

BACKGROUND: The medial prefrontal cortex plays a crucial role in regulating consciousness. However, the specific functions of its excitatory and inhibitory networks during anesthesia remain uncertain. Here, the authors explored the hypothesis that somatostatin interneurons in the medial prefrontal cortex enhance the effects of sevoflurane anesthesia by increasing γ-aminobutyric acid (GABA) transmission to pyramidal neurons. METHODS: Electroencephalography was utilized to reflect the depth of anesthesia. Immunostaining and fiber photometry were employed to assess neuronal activities and GABA delivery. The regulation of neuronal activity was achieved by chemogenetics and optogenetics. RESULTS: The expression of c-Fos was increased in somatostatin neurons of the medial prefrontal cortex during sevoflurane anesthesia (air vs. sevoflurane: 26.4 ± 6.5% vs. 48 ± 6.2%; P = 0.0007; n = 5 mice). Chemogenetic inhibition or activation of somatostatin neurons in the medial prefrontal cortex reduced (from 84 ± 24 s to 51 ± 18 s; P = 0.008; n = 7 mice) or prolonged (from 97 ± 31 s to 140 ± 30 s; P = 0.006; n = 7 mice) the sevoflurane anesthesia recovery time. Increased GABA input to pyramidal neurons in the medial prefrontal cortex precedes sevoflurane-induced loss of consciousness (baseline vs . pre-loss of the righting reflex: from 0.46 ± 0.57% to 2.25 ± 1.42%; P = 0.031; n = 10 mice). Activation of somatostatin neurons in the medial prefrontal cortex leads to a significant reduction in c...