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

听觉突触传递的缺陷导致听力损伤，而带状突触的退化发生在与年龄相关的听力损失中。了解内毛细胞（IHC）带状突触胞外分泌的不同阶段，以及确定年龄相关的带状退化过程中带状和突触后螺旋神经节神经元丢失之前IHC活动区的结构变化，是本研究的两个目的。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，并结合电子断层扫描对不同衰老阶段的ihc进行大体积3d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.