Mapping developmental maturation of inner hair cell ribbon synapses in the apical mouse cochlea
Mapping developmental maturation of inner hair cell ribbon synapses in the apical mouse cochlea
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DOI：
10.1073/pnas.1812029116
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发表时间：
2019-03-26
影响因子：
11.1
通讯作者：
Wichmann, Carolin
中科院分区：
文献类型：
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作者：
Michanski, Susann;Smaluch, Katharina;Wichmann, Carolin
耳蜗内毛细胞（IHC）的带状突触在听力开始前经历了分子组装和广泛的功能和结构成熟。在这里，我们使用电子显微镜和断层扫描以及Corti顶转器官的光学纳米显微镜表征了从出生前小鼠胚胎晚期（胚胎期14-18天）到成年期[出生后（P）48天]的IHC突触的纳米结构。我们发现，突触带前体到达突触前活动区（AZ）传入接触后，已经建立。这些带状前体含有蛋白质RIBEYE和piccolino，系链突触囊泡，它们的传递可能涉及活跃的基于微管的转运途径。突触接触经历从多个小AZ到一个单个大AZ的成熟转变。这种成熟的特征在于带前体与膜锚定带的融合，所述膜锚定带也似乎彼此融合。这种融合事件最常在P12左右遇到，因此与小鼠的听力开始一致。因此，这些事件可能是AZ的形态和功能成熟的基础。此外，突触后密度似乎经历了类似的细化与突触前成熟。在AZ成熟过程中发现的通过熔融的带状材料的快速添加可能代表调节带状物尺寸的一般机制。
Ribbon synapses of cochlear inner hair cells (IHCs) undergo molecular assembly and extensive functional and structural maturation before hearing onset. Here, we characterized the nanostructure of IHC synapses from late prenatal mouse embryo stages (embryonic days 14-18) into adulthood [postnatal day (P)48] using electron microscopy and tomography as well as optical nanoscopy of apical turn organs of Corti. We find that synaptic ribbon precursors arrive at presynaptic active zones (AZs) after afferent contacts have been established. These ribbon precursors contain the proteins RIBEYE and piccolino, tether synaptic vesicles and their delivery likely involves active, microtubule-based transport pathways. Synaptic contacts undergo a maturational transformation from multiple small to one single, large AZ. This maturation is characterized by the fusion of ribbon precursors with membrane-anchored ribbons that also appear to fuse with each other. Such fusion events are most frequently encountered around P12 and hence, coincide with hearing onset in mice. Thus, these events likely underlie the morphological and functional maturation of the AZ. Moreover, the postsynaptic densities appear to undergo a similar refinement alongside presynaptic maturation. Blockwise addition of ribbon material by fusion as found during AZ maturation might represent a general mechanism for modulating ribbon size.