Understanding synaptopathy at inner hair cell ribbon synapses on the ultrastructural level (A07)

听觉突触传递的缺陷会导致听力受损，在老年性听力损失期间会发生带状突触的退化。本研究的两个目的是了解内毛细胞(IHC)突触胞吐作用的不同阶段和确定IHC活动区的结构变化，这些变化先于IHC活动区和突触后螺旋神经节神经元在年龄相关的带状变性过程中的丢失。我们将结合光遗传学、高压冷冻和电子断层扫描对突触前蛋白的不同突变体进行研究，并将结合电子断层扫描对不同衰老阶段的IHC进行大规模三维超微结构重建。

Defects in auditory synaptic transmission cause hearing impairment, and a degeneration of ribbon synapses takes place during age-related hearing loss. Understanding different phases of exocytosis at inner hair cell (IHC) ribbon synapses and determining structural changes at IHC active zones that precede the loss of ribbons and postsynaptic spiral ganglion neurons during age-related ribbon degeneration are the two aims of this study. We will combine optogenetics with high-pressure freezing and electron tomography on different mutants of presynaptic proteins and will perform large volume 3D-ultrastructural reconstructions of IHCs in distinct stages of aging together with electron-tomography.