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

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 anesth...

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Published in:Molecular neurobiology 2023-10, Vol.60 (10), p.5789-5804
Main Authors: Yan, Jing, Hang, Bei-Ning, Ma, Lin-Hui, Lin, Jia-Tao, Zhou, Yue, Jiao, Xin-Hao, Yuan, Ying-Xuan, Shao, Ke-Jie, Zhang, Le-Meng, Xue, Qi, Li, Zi-Yi, Zhang, Hong-Xing, Cao, Jun-Li, Li, Shuai, Zheng, Hui, Wu, Yu-Qing
Format: Article
Language:English
Subjects:
Anesthesia
Biomedical and Life Sciences
Biomedicine
Brain slice preparation
c-Fos protein
Cell Biology
Firing rate
General anesthesia
Hypnosis
Immunofluorescence
Neurobiology
Neurology
Neurons
Neurosciences
Nucleus accumbens
Propofol
Sleep and wakefulness
Western blotting
γ-Aminobutyric acid
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Summary: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.
ISSN:0893-7648
1559-1182
DOI:10.1007/s12035-023-03445-1