神经元网络活动是神经系统功能的基础。近年来的研究发现神经元轴突起始段（axon initial segment，AIS）存在可塑性且可以感知网络活动的改变并调节神经元的兴奋性。但调控AIS可塑性的分子机制及其在疾病损伤中的作用尚待研究。本课题组前期研究发现：模拟缺血时AIS的结构会遭到破坏，而网络活动改变引起的分泌物质变化可以调控AIS的结构和功能。基于前期研究结果，拟利用电生理学、超高分辨成像及分子生物学等研究手段，从培养细胞、脑片组织、在体动物模型等多个层面研究神经元网络活动对AIS可塑性的影响，探索其分子机制；进而在缺血条件下改变调控AIS可塑性的分子通路，以期改善缺血后神经元网络重建和功能恢复，为脑缺血等疾病的临床治疗提供新思路。

Neuronal network activity is the basis for nervous system functions. Recent studies have found that the neuronal axon initial segment (AIS) is plastic which can sense the changes in network activity and regulate the excitability of neurons. However, the molecular mechanisms regulating AIS plasticity and its role in diseases are still need to be revealed. In our previous study, we found that AIS structure was destroyed under pathological conditions such as in vitro model of ischemia, while secreted molecules induced by network activity can regulate the structure and function of AIS. To further verify whether neuronal network activity under ischemia can affect AIS and cause neuronal damage, we plan to investigate how AIS plasticity is affected applying electrophysiological recordings and super resolution imaging. Furthermore, we will explore the underlying molecular mechanisms at different levels including cultured cells, brain tissue and in vivo animal model. Finally, we will manipulate AIS plasticity by interfering molecular pathways under the ischemia model, to improve neuronal network reconstruction and functional recovery after injury. We hope that understanding of AIS plasticity at the physiological and molecular levels could provide new insights to clinical application of ischemic diseases in the future.