ULTRASTRUCTURE OF AFFERENT INNERVATION AT INNER HAIR CELLS IN MOUSE

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 哺乳动物耳蜗传入神经支配的结构和生理机制在猫中仅被部分理解，在小鼠中基本上是未知的。随着小鼠作为听觉研究动物模型的重要性日益增加，有必要对内毛细胞（IHC），声音的转换器和听觉神经纤维之间的关键突触界面进行更详细的分析。在这个接口在C57 BL/6 J小鼠的传入终末和突触超微结构的初步研究揭示了两个形态上不同的传入末梢组。其中一个末端是传统的终扣，而另一个具有新的形态特征，包括明显由外膜内陷产生的深沟。这种末梢被称为折叠末梢，约占在8、16和32 kHz位点与IHC形成传入突触的末梢的一半。到目前为止，在研究的4只C57 BL/6 J小鼠中的3只中观察到了这种形态。我们提出了一项研究，其中电子断层扫描是用来阐明的三维结构的沟折叠终端，特别是它的关系，神经末梢的外膜。沟部分分隔终端，似乎隔离线粒体和其他细胞器。电子断层扫描将有助于深入了解这种不寻常结构的功能作用。 我们建议检查传入突触的组件，包括突触前体之间的空间关系，囊泡绑定到突触前膜和丝带。这项研究将提供有价值的信息，突触机制，并会发现立即使用正在进行的研究传入突触传递在这种动物。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The structure and underlying physiology of afferent innervation in the mammalian cochlea is only partially understood in cat and is essentially unknown in mouse. The increasing importance of mouse as an animal model in hearing research necessitates a more detailed analysis of the critical synaptic interface between the inner hair cell (IHC), the transducer of sound, and auditory nerve fibers. Preliminary studies of afferent terminal and synaptic ultrastructure at this interface in the C57BL/6J mouse have revealed two morphologically distinct groups of afferent endings. One of these endings is a conventional bouton, whereas the other has novel morphological features including the presence of a deep sulcus apparently created by the invagination of the outer membrane. This ending has been called the folded ending and accounts for about a half of the terminals that form afferent synapses with IHCs at 8, 16 and 32 kHz sites. This morphology has been observed in 3 out of 4 C57BL/6J mice studied so far. We propose a study in which electron tomography is used to elucidate the 3-dimensional structure of the sulcus in folded terminals and particularly its relationship to the outer membrane of the nerve terminal. The sulcus partially compartmentalizes the terminal and appears to sequester mitochondria and other organelles. Electron tomography would be helpful in providing insight into the functional role of this unusual structure. We propose to examine the spatial relationships between components of the afferent synapse including the pre-synaptic body, and vesicles bound to both the pre-synaptic membrane and ribbon. This study will provide valuable information about the synaptic machinery and would find immediate use in on-going studies of afferent synaptic transmission in this animal.