全麻对婴幼儿神经发育的影响广受关注，然而其机制远未阐明。研究发现海马突触结构和功能发育异常参与认知行为损伤。我们前期研究亦发现重复七氟醚暴露导致海马锥体神经元兴奋性突触结构及功能异常，提示海马锥体神经元兴奋性突触发育异常可能是认知障碍的发生原因，但海马兴奋性突触发育异常的特征与机制，及在认知障碍中的作用仍需深入研究。同源结构域相互作用蛋白激酶2（HIPK2）作为转录因子和信号转导子可调节Wnt/β-catenin通路，抑制细胞增殖和存活，而经典的Wnt通路被证实参与兴奋性突触的发育和成熟。因此，本项目拟以幼鼠重复七氟醚暴露模型为基础，综合应用神经发育、电生理、化学遗传等技术，系统研究七氟醚暴露致海马锥体神经元兴奋性突触结构和功能发育异常，并探讨其分子机制，为进一步阐明全麻的复杂机制提供支持，最终为安全实施小儿麻醉提供理论依据。

The influence of general anesthesia on neurodevelopment of infants and young children is becoming a heath problem which attracts public attentions. However, the underlying mechanisms are far from being elucidated. Several studies have suggested that synaptic structure and function abnormalities involving in the hippocampus cognitive impairment. Our preliminary research found that neonatal exposure to Sevoflurane induce the abnormality of excitatory synaptic in hippocampal pyramidal neurons, which suggested that cognitive dysfunction may be caused by the developmental abnormality of excitatory synaptic in hippocampal pyramidal neurons. However the characteristics and mechanisms of developmental abnormalities of hippocampal excitatory synaptic and their roles in cognitive dysfunction still need to be further studied. As the transcription factor and the signal transducer, homeodomain interacting protein kinase 2(HIPK2) can regulate the wnt/beta-catenin signaling and inhibite cell proliferation and survival. And Wnt pathways have been confirmed to participate in the development and maturation of excitatory synapses. Based on the neonatal sevoflurane inhalation model, the present study aims to observe the detailed developmental changes and reveal the molecular mechanisms in excitatoy synaptic, combining with multiple techniques including neurodevelopment, electrophysiology and chemogenetics. Meanwhile our study could provide further support for the clarification of mechanisms underlying general anesthetics-induced neurodevelopmental disorder and ultimately provide a theoretical basis for improved clinical pediatric anesthesia.