CaMKII磷酸化对氟醚类吸入麻醉皮层/皮层下信息解偶联与再整合的调控及机制

fMRI studies indicated that Decrease of functional connectivity and information unbinding ocurrs at unconciousness induced by inhalational anesthsia, but how does it ocurr and whether a anatomy connectivity exist remains largely unknown. Our recent studies showed that a reversible inhibition of CaMKII phosphorylation occurs during inhalational anesthesia-recovery cycle and the inhibitor/activator of CaMKII cause the change of the time of loss of righting reflex (LORR) and its recovery. It was reported that CaMKII, an important protein kinase in the brain, is involved in regulating a variety of nervous function, including learning, memory consolidation,even sleep-arousal state by modulation on GABA and Ach neurotransmitter synthesis and release at synapse. it was also clarified that GABA and Ach in sleep-arousal circuit, is seriously involved in unconciousness induced by volatile anesthetics. According to these previous findings, our hypothesis is: CaMKII phosphorylation plays an important role in functional connectivity decrease and information unbinding during general anesthesia by regulating the balance of GABA and Ach transmitter system in sleep-arousal circuit. So this project is aimed to investigate how CaMKII effect the functional connectivity and information unbinding by modulating GABA(VLPO) and Ach(PPTg) transmitter system in sleep-arousal circuit in inhalational anesthesia with fMRI and optogenetics techniques. The results from this study will be helpful to clarifying the mechanism of unconciousness induced by general anesthesia.

fMRI研究发现吸入麻醉可诱导皮层及皮层下功能性连接减弱、信息解偶联及再整合障碍，但其分子及神经环路机制尚不清楚。我们研究发现吸入麻醉-苏醒过程中脑内CaMKII磷酸化水平发生可逆性抑制改变，并影响全麻意识消失与恢复过程；已知CaMKII可在突触水平对GABA/Ach进行调控参与学习与记忆，甚至可调控睡眠与觉醒；而睡眠觉醒通路中GABA/Ach均与全麻意识消失密切相关。由此我们推测：CaMKII磷酸化可能通过对脑内GABA/Ach的调节参与吸入麻醉信息解偶联和再整合的调控。本项目拟用fMRI及光遗传学技术探讨吸入麻醉中选择性调控睡眠觉醒通路中GABA（VLPO）/Ach（PPTg）神经元活性及CaMKII磷酸化水平对皮层信息解偶联及再整合的影响，用微透析及电生理技术探讨CaMKII对相应核团中GABA/Ach神经元递质释放及突触电信号的调控作用，明确CaMKII调控全麻意识状态的可能机制。