The mechanism by which general anesthetic drugs modify the state of consciousness remains unidenti ed. In essence, the Nucleus Accumbens(NAc)may be directly engaged in the principle of general anesthesia. However, it is uncertain whether NAc GABAergic neurons play a role in the propofol-induced general anesthesia effect. MethodsWe used immuno uorescence and Western blotting to access the activities of NAc GABAergic neurons during propofol anesthesia, and then we utilized chemogenetic and optogenetic methods to investigate the necessity of NAc GABAergic neurons in the change of consciousness. Moreover, we also conducted behavioral tests to analyze anesthetic induction and emergence. ResultsWe found out that c-Fos expression was considerably dropped in NAc GABAergic neurons after propofol injection. 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. ConclusionsOur results demonstrate that NAc GABAergic neurons modulate induction and emergence of propofol anesthesia. | BackgroundGeneral anesthesia is a reversible condition of unconsciousness induced by anesthetic medications, which have been commonly used in clinical surgery for almost two hundred years [1]. Particularly, the mechanism by which general anesthetic drugs unleash the general anesthesia effect and ulteriorly modify the state of consciousness remains unidenti ed [2]. When general anesthetic drugs are applied for operations, patients frequently have adverse reactions such as low blood pressure, respiratory depression, delayed waking, and even death [3]. Additionally, cognitive dysfunction and stress disorder are likely to be continually companied by patients for a long period [4]. Unfortunately, few effective treatments exist for these debilitating illnesses, accounting for the uncertain mechanism of general anesthesia [2]. As a result,

It has been widely demonstrated by numerous preclinical studies and clinical trials that the neonates receiving repeated or long-time general anesthesia (GA) could develop prolonged cognitive dysfunction. However, the definite mechanism remains largely unknown. Epigenetics, which is defined as heritable alterations in gene expression that are not a result of alteration of DNA sequence, includes DNA methylation, histone post-translational modifications, non-coding RNAs (ncRNAs), and RNA methylation. In recent years, the role of epigenetic modifications in neonatal GA-induced neurotoxicity has been widely explored and reported. In this review, we discuss and conclude the epigenetic mechanisms involving in the process of neonatal anesthesia-induced cognitive dysfunction. Also, we analyze the wide prospects of epigenetics in this field and its possibility to work as treatment target.

Introduction: The mechanism by which general anesthetic drugs modify the state of consciousness remains unidentified. In essence, the Nucleus Accumbens(NAc)may be directly engaged in the principle of general anesthesia. However, it is uncertain whether NAc GABAergic neurons play a role in the propofol-induced general anesthesia effect. Methods We used immunofluorescence and Western blotting to access the activities of NAc GABAergic neurons during propofol anesthesia, and then we utilized chemogenetic and optogenetic methods to investigate the necessity of NAc GABAergic neurons in the change of consciousness. Moreover, we also conducted behavioral tests to analyze anesthetic induction and emergence. Results We found out that c-Fos expression was considerably dropped in NAc GABAergic neurons after propofol injection. 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. Conclusions Our results demonstrate that NAc GABAergic neurons modulate induction and emergence of propofol anesthesia.