神经活动对突触囊泡内吞带时空特性的调控

突触囊泡循环是保证神经系统持续活动的重要机制。囊泡内吞回收是其循环中不可或缺的环节。突触内吞带是囊泡回收的结构基础，它的时空特性直接决定着预备回收囊泡的内吞方式和效率，影响着突触短时程可塑性和信息处理。然而，由于研究方法和标本的限制，突触终末上内吞带的空间分布和对应于不同神经活动的动态变化规律以及与突触活性带的偶联关系至今尚未被揭示。基于申请人的前期积累，结合神经电生理/神经影像学方法取得的最新进展，本项目拟以小鼠calyx of Held突触为研究对象，结合对突触前膜电容的检测，光遗传学刺激及特异性荧光标记等方法，实现对突触囊泡内吞带的时空特性的完整解析。我们将在本项目中完成对突触内吞带时空特性的直接观测，定量分析突触内吞带与活性带的偶联关系，并阐明神经活动对突触内吞带时空特性的调控作用，为探索突触内吞带在各种神经活动中维持高效、稳定的突触传递的机制和作用提供新的洞察。

Synaptic vesicle recycling is pivotal for maintaining reliable synaptic transmission. Synaptic vesicle endocytosis is a necessary process of vesicle recycling. Synaptic endocytic zone is the fundamental structure of vesicle retrieval, and its spatio-temporal feature determines the pathway and efficiency of endocytosis, affecting the short term plasticity and information processing. However, few relative studies could give an accurate description of the dynamic changes of the endocytic zone corresponding to neuronal activities and the coupling relationship between active zone and endocytic zone, because of the limitation of study materials and methods. Based on our previous study, we will take advantages of the research progress of electrophysiology and neuroimaging, apply mice calyx of Held synapse as our study objects, record the presynaptic membrane capacitance, and combine optogenetics stimulation and fluorescence labeling methods, so as to completely analyze the spatio-temporal features of synaptic endocytic zone. This study would provide the first directly observation of synaptic endocytic zone, quantitatively describe the coupling relationship between active zone and endocytic zone, elucidate the regulation of neuronal acitivities on synaptic endocytic zone and shed new insight into the impact of the synaptic endocytic zone on stable and reliable synaptic transmission under variable levels of neuronal activity.