Piccolino调控CaV1.3分布影响Ribbon突触的时间信息处理能力

Ribbon突触对刺激信号所展现的神经递质不同程度快速、精确的释放是耳蜗听觉信号处理的关键，而其特殊的分子组成是实现这些功能的基础。阐明这些蛋白的功能，对于理解其快速响应功能的机制至关重要。Piccolino是短的Piccolo变异体，是Ribbon突触的骨架蛋白，其功能尚不清楚。项目组前期研究中成功构建了Piccolino基因敲除小鼠，预实验提示Piccolino敲除小鼠与正常小鼠具有相同的听觉阈值，但时间信息处理能力明显下降。这可能与Piccolino调控钙离子通道的分布影响Ribbon突触时间信息处理能力有关。本项目拟在前期研究的基础上，探讨Piccolino敲除对小鼠听觉功能的影响；明确Piccolino敲除小鼠Ribbon突触重要蛋白的变化；确证在体听神经单纤维放电率及离体内毛细胞膜电容的变化，从而明确Piccolino敲除对Ribbon突触时间信息处理能力的影响。

The rapid and accurate release of neurotransmitters from Ribbon synapses by different degrees is the key to the auditory signal processing, and its special molecular composition is the basis for achieving these functions. Elucidating the.functions of these proteins is essential for understanding the mechanism of their rapid response function. Piccolino is a short variant of Piccolo and the skeleton protein of Ribbon synapse. Its function is not yet clear. We successfully constructed Piccolino knockout mice in the previous study. The results indicated that Piccolino knockout mice had the same auditory threshold as normal mice, but the temporal information processing capacity decreased significantly. This may be related to the regulation the distribution of calcium channels by Piccolino. On the basis of previous studies, this project intends to explore the effects on the auditory function of Piccolino knockout mice; to clarify the changes of important Ribbon synaptic proteins; to confirm the changes of discharge rate of single auditory nerve fibers in vivo and capacitance of hair cell membrane in vitro, so as to clarify the effects and mechanisms of Piccolino knockout on the temporal information processing capacity of Ribbon synapse.