锥体神经元轴突起始段（axon initial segment, AIS）是动作电位起始发放的位置,有且仅接收来自吊灯样细胞（chandelier cell，ChC）的突触联系。然而，ChC选择性支配AIS的机制目前并不清楚。申请人最新工作发现，锥体神经元AIS表达的L1CAM细胞黏附分子对ChC支配AIS是必需的；同时，敲除锥体神经元细胞骨架蛋白βII-Spectrin会导致ChC错误地支配到其它区域。这些结果提示，AIS上的吸引信号通过与ChC轴突末端细胞黏附分子相互识别介导ChC支配AIS，而锥体神经元胞体和树突上的抑制信号确保ChC不支配AIS以外的区域，吸引和抑制信号的同时存在为ChC精确定位提供双重保障。本项目将综合运用分子生物学、影像学、小鼠遗传学和化学遗传等多学科研究手段进一步解析ChC选择性支配AIS的机制，为理解中间神经元微环路的正确建立提供新的思路。

Axon initial segment (AIS) is the proximal compartment of axon where action potential is initiated. It receives GABAergic synaptic input exclusively from chandelier cell (ChC). However, how ChC selectively innervates AIS is not known. The applicant has found that AIS L1CAM is required for ChC innervation on AIS. Moreover, knockdown of pyramidal neuron cytoskeleton protein βII-spectrin results in mistargeting of ChC outside of AIS. These results indicate that the attractive signals on AIS mediate the recognition of ChC axonal terminals and AIS adhesion molecules, whereas the repulsive signals on cell body and dendrites restrict the ChC innervation on AIS only. Both attractive signal and repulsive signal are essential for ChC chandelier cell to selectively innervate on AIS. By combining molecular biology, mouse genetics, morphologic analysis and chemo-genetics, the applicant will investigate the molecular mechanism that regulate ChC selectively targeting on AIS. Addressing these questions will advance our understating of how interneuron microcircuits assembly are regulated.