听觉毛细胞带状突触上钙信号的精准调控机制

在包括声音定位和频率辨别的多数听觉感受中，听觉传入纤维上动作电位的发放必须具备高达微秒级的超高时间精度。因为这些动作电位都是听觉毛细胞以突触囊泡释放的方式激活听觉传入纤维而发放的，这就要求听觉毛细胞上的突触囊泡释放能够被精确控制。与中枢神经系统里的神经元相类似，听觉毛细胞上的突触囊泡释放也是由胞内钙信号所触发的，但这些钙信号的精准调控机制一直以来都不清楚。这其中的主要原因就在于前人的研究结果都是在听觉系统发育不完全的幼年动物上完成的。在本研究课题里，我们将在成年牛蛙的听觉器官里精确测量听觉毛细胞上钙通道的生物物理特性，钙通道与突触囊泡之间的平均耦合距离，以及胞内钙离子移除的速率。通过比较在不同特征频率的听觉毛细胞上得到的这些研究结果，我们能够深入了解听觉毛细胞内的钙信号是如何能够在一个声音周期里高效、快速地变化，从而能为听觉信息提供足够高的时间精度。

In normal hearing, e.g. localizing sounds or discriminating frequencies, auditory afferent fibers must fire action potentials with extraordinary temporal precision, up to 10 ns. Given that all these action potentials are triggered by synaptic vesicle releases from auditory hair cells, exocytosis from auditory hair cells must be precisely controlled. Like exocytosis from neurons in the central nervous system, synaptic vesicle releases from auditory hair cells are also triggered by intracellular Ca2+ signals, but the molecular and cellular mechanisms underlying these Ca2+ signals are largely unknown. This is because previous studies were all conducted in immature hearing organs from young animals. In this research project, we will use the amphibian papilla from adult bullfrogs and examine the Ca2+ channel properties, the coupling distance between Ca2+ channels and synaptic vesicles, and the removal of intracellular Ca2+ ions. By comparing results from auditory hair cells at different characteristic frequencies, we will be able to gain insights into the rapid rise and decay of Ca2+ signals within a single acoustic cycle, which are critically required for auditory afferent fibers to fire action potentials with enough temporal precision that is necessary for normal auditory perception.