七氟烷多次麻醉致乳鼠远期认知功能损伤是麻醉学颇具挑战和争论的课题。我们前期研究提示：星形胶质细胞介导的突触功能异常在此种认知损伤中发挥重要作用，但发生机制不清。鉴于：1）星形胶质细胞为γ振荡产生提供合适的环境使神经元放电活动同步性增加从而调节突触可塑性，其功能异常可致认知损伤；2）神经连接蛋白-1（neuroligin-1,NL-1）与突触前轴突蛋白 1β（neurexin-1β,Nrx-1β）跨突触结合，动态调节兴奋性突触的可塑性；3）七氟烷麻醉后星形胶质细胞分泌Hevin减少，后者特异性桥接Nrx-1β/NL-1。我们推测麻醉后星形胶质细胞损伤，Hevin分泌减少，Nrx-1β/NL1跨突触相互作用减弱，继而影响兴奋性突触功能，最终导致γ振荡异常及认知损伤。本研究拟通过应用分子生物学、转基因及电生理等技术，从“分子-突触-神经环路-整体行为”多层次揭示七氟烷致乳鼠认知损伤的新机制。

Repeated exposure to sevoflurane induced long-term cognitive impairment in neonatal rats is a challenging and controversial research topic currently. Our previous studies have shown that astrocytes-mediated abnormal synaptic function plays a key role in anesthesia of sevoflurane induced long-term cognitive impairment in neonatal rats, yet the underlying mechanisms remain unclear. Based on the following findings: 1) Astrocytes provide a suitable environment for the generation of γoscillations, which increase the firing synchronicity of neurons and thus regulate synaptic plasticity; 2) neuroligin-1(NL1) binds with neurexin-1β (Nrx-1β) across synapses and dynamically shapes excitatory synaptic efficacy and plasticity; 3) the secretion of Hevin was reduced after repeated exposure to sevoflurane, which specifically bridges the interaction of Nrx-1β/NL1. Therefore, we hypothesize that repeated exposure to sevoflurane damages astrocytes and consequently reduces the secretion of Hevin, contributing to weakens the transsynaptic interaction of Nrx-1β/NL1, which then affects the function of excitatory synapses, and finally leads to abnormal γoscillations and cognitive impairment.. For these purposes, we will apply molecular biology, transgenic, and electrophysiological techniques to reveal the new mechanisms underlying anesthesia of sevoflurane-induced cognitive impairments in neonatal rats in terms of molecules – synapses - neural circuit - overall behaviors. This work will provide the theoretical basis and interventional targets for the prophylaxis and treatment of cognitive impairment induced by anesthesia of sevoflurane in neonatal rats.