ULTRASTRUCTURE OF AFFERENT INNERVATION AT INNER HAIR CELLS IN MOUSE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 哺乳动物耳蜗神经传入神经的结构和基本生理在猫中只有部分了解，在小鼠中基本上是未知的。小鼠在听力研究中作为动物模型的重要性日益增加，因此有必要对内毛细胞(IHC)、声音传导者和听神经纤维之间的关键突触界面进行更详细的分析。对C57BL/6J小鼠这一界面的传入终末和突触超微结构的初步研究揭示了两组在形态上截然不同的传入末梢。其中一个是传统的末端，而另一个具有新奇的形态特征，包括明显由外膜内陷造成的深沟的存在。这种末端被称为折叠末端，约占在8、16和32 kHz处与IHC形成传入突触的终末的一半。到目前为止，在所研究的4只C57BL/6J小鼠中，有3只观察到了这种形态。我们建议使用电子断层扫描来阐明折叠终末中沟的三维结构，特别是它与神经末梢外膜的关系。沟将终末部分隔开，似乎隔离了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的结构的功能作用。我们建议研究包括突触前小体在内的传入突触组件之间的空间关系，以及与突触前膜和突触带结合的囊泡。这项研究将提供有关突触机制的有价值的信息，并将立即用于正在进行的该动物传入突触传递的研究中。

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.