GABAergic Neurons in the Nucleus Accumbens are Involved in the General Anesthesia Effect of Propofol

加巴能 异丙酚 光遗传学 伏隔核 神经科学 麻醉剂 麻醉 荷包牡丹碱 药理学 医学 γ-氨基丁酸受体 生物 中枢神经系统 抑制性突触后电位 内科学 受体
作者
Jing Yan,Bei-Ning Hang,Lin-Hui Ma,Jia-Tao Lin,Yue Zhou,Xin-Hao Jiao,Ying-Xuan Yuan,Ke-Jie Shao,Lemeng Zhang,Qi Xue,Ziyi Li,Hongxing Zhang,Jun‐Li Cao,Shuai Li,Hui Zheng,Yuqing Wu
出处
期刊:Molecular Neurobiology [Springer Nature]
卷期号:60 (10): 5789-5804 被引量:5
标识
DOI:10.1007/s12035-023-03445-1
摘要

The mechanism underlying the hypnosis effect of propofol is still not fully understood. In essence, the nucleus accumbens (NAc) is crucial for regulating wakefulness and may be directly engaged in the principle of general anesthesia. However, the role of NAc in the process of propofol-induced anesthesia is still unknown. We used immunofluorescence, western blotting, and patch-clamp to access the activities of NAc GABAergic neurons during propofol anesthesia, and then we utilized chemogenetic and optogenetic methods to explore the role of NAc GABAergic neurons in regulating propofol-induced general anesthesia states. Moreover, we also conducted behavioral tests to analyze anesthetic induction and emergence. We found out that c-Fos expression was considerably dropped in NAc GABAergic neurons after propofol injection. Meanwhile, patch-clamp recording of brain slices showed that firing frequency induced by step currents in NAc GABAergic neurons significantly decreased after propofol perfusion. Notably, chemically selective stimulation of NAc GABAergic neurons during propofol anesthesia lowered propofol sensitivity, prolonged the induction of propofol anesthesia, and facilitated recovery; the inhibition of NAc GABAergic neurons exerted opposite effects. Furthermore, optogenetic activation of NAc GABAergic neurons promoted emergence whereas the result of optogenetic inhibition was the opposite. Our results demonstrate that NAc GABAergic neurons modulate propofol anesthesia induction and emergence.
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