Study On The Changes Of Different Neurotransmitter Concentrations In The Cortex Under General Anesthesia

Background: General anesthesia is widely applied in clinical practice,however,the precise mechanism of consciousness loss induced by general anesthetics remains unknown.None of the previous hypotheses on the mechanism of general anesthesia can fully explain anaesthetic-induced loss of consciousness(a LOC).In recent years,more and more researchers have suggested that neuronal network synchronization is a possible mechanism of a LOC.The activity of neural network is mainly regulated by neurotransmitter network,so the synchronization of neural network may be caused by the synchronization of neurotransmitter network.The synchronization of neurotransmitter network means that the changes of neurotransmitter show synchronicity,so it is very important to determine whether the changes of neurotransmitter are synchronized.A variety of neurotransmitters are involved in a LOC,and the neurotransmitter network composed of these neurotransmitters acts on the neuronal network to produce LOC.Gamma-aminobutyric acid(GABA),glutamate(Glu),norepinephrine(NE),acetylcholine(Ach)and dopamine(DA)played an important role in sleep/wake and LOC processes.The medial prefrontal cortex(m PFC)and primary visual cortex(V1)were important target areas of a LOC.Therefore,identifying the immediate changes in m PFC and V1 of the above five neurotransmitters during a LOC may help us to uncover the neural mechanism of a LOC.There are many general anesthetics that can cause a LOC,of which the intravenous anesthetic propofol and the inhalation anesthetic sevoflurane are the most commonly used in the clinic.Therefore,this study aims to use tools to observe the immediate changes of five neurotransmitters,GABA,Glu,NE,Ach and DA,in m PFC and V1 under propofol and sevoflurane anesthesia,and analyze whether the neurotransmitter network composed of these five neurotransmitters is synchronized,in order to reveal that the synchronization of neurotransmitter network is one of the possible mechanisms of a LOC.Methods: In the study of m PFC brain region,C57BL/6J mice aged 8-10 weeks were randomly divided into intrabitoneal injection group: normal saline group(100ml/kg),propofol group(25,100,200mg/kg),inhalation group: air group,sevoflurane group(0.3%,3%,5%).In the study of V1 brain region,intrabitoneal injection treatment group:normal saline group(100ml/kg),propofol group(100mg/kg),inhalation treatment group:air group,sevoflurane group(3%),and other treatments were the same as m PFC brain region.The 25 mice in each group were randomly divided into 5 groups and injected with GABA,Glu,NE,Ach and DA neurotransmitter sensors into their respective target brain regions and implanted with optical fiber cannula.The immediate changes of GABA,Glu,NE,Ach and DA in the target brain regions of mice in each treatment group were detected by in vivo fibrophotometry after a 2-3 week recovery period and a3 day adaptation period.Finally,the correlation between the m PFC and the five neurotransmitters in V1 was analyzed.Results: In 100ml/kg normal saline,25mg/kg propofol,air and 0.3% sevoflurane group,the concentrations of GABA,Glu,NE,Ach and DA in m PFC and V1 of mice had no significant changes compared with those before treatment.In 100mg/kg and 200mg/kg propofol groups,the concentrations of GABA,Glu,NE and Ach in m PFC and V1 of mice increased in a dose-dependent manner compared with those before treatment.In100mg/kg propofol group,the concentrations of DA in m PFC and V1 of mice had no significant changes compared with those before treatment.In 200mg/kg propofol group,the concentrations of DA in m PFC and V1 were significantly increased compared with those before treatment.In 3% and 5% sevoflurane groups,the concentrations of GABA,Glu,NE and Ach in m PFC and V1 of mice were reduced in a dose-dependent manner compared with before treatment.The five neurotransmitters in m PFC and V1 were highly correlated in 100mg/kg,200mg/kg propofol and 3% and 5% sevoflurane treatment groups.Conclusion: Synchronization of cortical neurotransmitter networks may be one of the mechanisms of a LOC.