Role of the ribbon synapse in high-frequency neural phase locking

在具有良好低频听力的人类和动物中，听觉神经传入纤维的锁相被认为是中枢听觉系统的一个显著的时间编码。锁相听觉神经纤维中峰值的时间色散可低至30µs。这代表了其极端的超快和时间精确的信息处理。然而，潜在的细胞机制尚不清楚。本项目旨在探讨毛细胞带突触在这一过程中的具体作用。之所以选择鸡作为模型生物，是因为鸡具有以下特点：1)强大的听觉神经锁相功能（khz范围）；2)在卵细胞的早期胚胎阶段，对已建立的病毒介导的基因错误表达技术具有良好的可及性。我们有一只鸡模型，它的一只耳朵上有一种异常表型，这种表型特异性地改变了毛细胞及其神经支配，从而增加了连接每条传入纤维的突触带的数量。这将允许测试最近提出的机制，即紧密同步的多泡递质释放对于在神经相位锁定中观察到的正常时间精度至关重要。我们预测，特别是在锁相的频率上限附近，带状位点数量的增加将降低同步，从而降低尖峰的时间精度。这将在体内用几个指标进行量化。我们的鸟类工作将通过扩展概念和可用工具箱来补充正在进行的小鼠毛细胞工作，以揭示听觉通路中这个非常专门的第一突触的超快处理机制。

In humans and animals with good low-frequency hearing, phase locking by the afferent fibres of the auditory nerve is known to be a salient temporal code for the central auditory system. The temporal dispersion of spiking in phase-locking auditory-nerve fibres can be as low as 30 µs. This represents ultrafast and temporally precise information processing at its extreme. However, the underlying cellular mechanisms are not well understood. This project aims to explore the specific role of the hair-cell ribbon synapse in this process. The chicken is chosen as the model organism because it combines 1) robust auditory-nerve phase-locking into the kHz-range with 2) good accessibility of early embryonic stages in-ovo for established techniques of virus-mediated gene misexpression. We have a chicken model available with an aberrant phenotype in one ear that specifically changes the hair cells and their innervation, such that an increased number of synaptic ribbons connects to each afferent fibre. This will allow for testing the recently suggested mechanism that tightly synchronised multi-vesicular transmitter release is crucial for the normal temporal precision observed in neural phase locking. We predict that, especially near the upper frequency limit of phase locking, an increased number of ribbon sites will degrade the synchronisation and thus degrade the temporal precision of spiking. This will be quantified with several metrics in vivo. Our bird work will complement ongoing work on mouse hair cells by extending the concepts and available toolbox for unravelling the mechanisms for ultrafast processing at this very specialised first synapse in the auditory pathway.