MORPHOLOGY AND CONNECTIONS OF THE SPIRAL GANGLION

拟议的研究解决了有关基本的未解决的问题， 耳蜗螺旋神经节的组织及其对耳蜗的输入 脑干 用猫作为动物模型， 成熟耳蜗的神经元布线的概念将得到证实， 重新检查。 听觉诱发反应，生理反应 微电极记录和细胞化学标记技术，沿着 将采用广泛的光学和电子显微镜分析。 将特别注意的形态和连接的 小的无髓鞘II型神经节细胞，与更多的 常见的I型细胞：a）神经元的超微结构特征 这两种细胞类型的过程将在连续重建中定义 B）两个神经元的差异投影 特定的耳蜗核亚群和细胞场将 进一步划定;和3）个别神经元支配内部和 用辣根过氧化物酶（HRP）标记的外毛细胞， 追踪和精细结构的父母螺旋神经节细胞 定义了 在其他实验中， 螺旋神经节细胞超微结构的病理变化 继发于硫酸新霉素对毛细胞的破坏， 检查，和残留的螺旋神经节细胞的中央投影， 将描绘严重病理性耳蜗。 这些研究应 更好地了解影响耳蜗神经功能的因素， 退化，并可能有重要的影响，重新的疗效， 人工耳蜗植入患者并行耳病理。 此外，本发明还 毛细胞中的囊泡运输将进一步表征为： 从外淋巴摄取HRP的研究。 证据表明，HRP摄取可能是 将评估活动依赖性。 最后，一种新的细胞化学探针 （新霉素与HRP和胶体金结合）将用于 证明了新霉素膜受体的胞内位点， 定义负责钙螯合的膜成分。 这些 研究应该有助于我们理解细胞机制 新霉素耳毒性，并提供了新的见解的基础细胞生物学 哺乳动物的毛细胞。

The proposed studies attack unresolved questions about the fundamental organization of the cochlear spiral ganglion and its input to the brainstem. Using the cat as the animal model, certain inadequately substantiated concepts of the neuronal wiring of the mature cochlea will be re-examined. A combination of auditory evoked response, physiological microelectrode recording and cytochemical labeling techniques, along with extensive light and electron microscopic analysis will be employed. Special attention will be given to the morphology and connections of the small unmyelinated type II ganglion cells as contrasted with the more common type I cells: a) Ultrastructural characteristics of the neuronal processes of the two cell types will be defined in serial reconstructions of electron images; b) The differential projections of the two neuronal populations to specific cochlear nucleus subdivisions and cell fields will be further delineated; and 3) Individual neurons innervating inner and outer hair cells and labeled with horseradish peroxidase (HRP), will be traced and the fine structure of their parent sprial ganglion cells defined. In other experiments, the time course and sequence of ultrastructural pathological alternations in spiral ganglion cells secondary to destruction of the hair cells by neomycin sulfate will be examined, and the central projections of residual spiral ganglion cells in severely pathological cochleae will be delineated. These studies should provide a better understanding of factors precipatating cochlear neural degeneration and may have important implications re the efficacy of a cochlear implant in patients with parallel otic pathologies. Additionally, a vesicular transport in the hair cells will be further characterized in studies of HRP uptake from the perilymph. Evidence that HRP uptake may be activity dependent will be evaluated. Finally, a new cytochemical probe (neomycin conjugated to HRP and colloidal gold) will be employed to demonstrate the intracochlear sites of neomycin membrane receptors and to define membrane constituents responsible for calcium sequestration. These studies should contribute to out understanding of the cellular mechanisms of neomycin ototoxicity and provide new insight into the basic cell biology of mammalian hair cells.