Single-cell Marking Studies of the Auditory Nerve

听觉神经的单细胞标记研究

• 批准号: 7649911
• 负责人: DAVID K. RYUGO
• 金额: $ 67.46万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7649911
• 关键词: Acoustic Nerve; Acoustics; Affect; Antibodies; Auditory; Auditory Brain Stem Implants; Auditory system; Bilateral; Bionics; Brain; Brain Stem; Cell Nucleus; Cells; Child; Cochlear Implants; Cochlear implant procedure; Cochlear nucleus; Code; Contralateral; Cues; Data; Dendrites; Development; Discrimination; Electron Microscopy; Employee Strikes; Felis catus; Fostering; Foundations; Gifts; Goals; Hearing; Hearing Impaired Persons; Implant; Inherited; Knowledge; Lateral; Light; Medial; Mediating; Microscopic; Nerve Endings; Neurons; Noise; Olives - dietary; Pathway interactions; Play; Population; Presynaptic Terminals; Process; Reaction; Recovery; Research; Role; Shapes; Signal Transduction; Sound Localization; Speech; Staging; Structure; Synapses; Synaptic Vesicles; Synaptic plasticity; Testing; Time; Work; auditory pathway; binaural hearing; cell type; congenital deafness; deafness; density; effective therapy; experience; immunocytochemistry; improved; information processing; lateral superior olive; miniaturize; neural circuit; neuronal cell body; postsynaptic; response; restoration; skills; sound; superior olivary nucleus; theories; trapezoid body; treatment strategy

Hearing plays an important role in the normal development of brain structure and function. We have shown that hereditary congenital deafness in cats results in abnormal synaptic structure in auditory nerve terminals, and that synaptic rescue occurs after providing young cats with cochlear implants (Ryugo et al. 2005). These affected synapses initiate circuits implicated in the processing of binaural cues, and will be the subject of the proposed research. Our studies will contribute to knowledge about synaptic plasticity and be pertinent to the increasing number of bilateral cochlear implants that seek to restore the functional benefits of binaural hearing. In theory, bilateral cochlear implants should enrich the acoustic experience by providing cues that contribute to sound localization. Better azimuthal sound localization skills should improve signal discrimination in noise, enhance sound quality, and foster better speech understanding. The brain circuits that mediate these binaural functions are initiated by two classes of auditory nerve endings that in turn establish two separate pathways in the brainstem. One path extracts interaural time differences, whereas the other is specialized for processing interaural intensity differences. Over the next two years, we propose two specific aims to explore the synaptic organization of excitatory and inhibitory inputs involved with these binaural circuits. We will characterize and quantify afferent terminals using electron microscopy and immunocytochemistry to test specific hypotheses regarding how congenital deafness affects binaural circuits by comparing data from normal hearing cats and congenitally deaf cats with or without a cochlear implant. The focus will be on spherical bushy cells and their projections to principal cells of the lateral and medial superior olive, and on globular bushy cells that project to the principal cells of the medial nucleus of the trapezoid body. These aims will evaluate the effect of stimulation via cochlear implants on brain plasticity, and test the hypothesis that some auditory circuits are more amenable to recovery than others. This research utilizes a unique colony of cats expressing hereditary deafness and the generous gift of bilateral cochlear implants from Advanced Bionics Corporation. The results will advance our understanding of the role of cochlear implants and deafness on brain plasticity. The data may also help explain why interaurallevel differences are more salient to bilateral implant users than interaural timing differences. Lastly, the new knowledge could contribute to improved treatment strategies for users of bilateral cochlear implants and impact considerations of auditory brainstem implants.

听力对于大脑结构和功能的正常发育起着重要作用。我们已经证明，猫的遗传性先天性耳聋会导致听觉神经末梢的突触结构异常，并且在为幼猫植入人工耳蜗后会发生突触挽救（Ryugo et al. 2005）。这些受影响的突触启动与双耳线索处理有关的电路，并将成为拟议研究的主题。我们的研究将有助于增进有关突触可塑性的知识，并与越来越多的双边人工耳蜗植入物相关，这些植入物旨在恢复双耳听力的功能优势。 理论上，双侧人工耳蜗应该通过提供有助于声音定位的线索来丰富声音体验。更好的方位声音定位技能应该可以改善噪声中的信号辨别能力，提高音质，并促进更好的语音理解。介导这些双耳功能的大脑回路是由两类听觉神经末梢启动的，而这两类听觉神经末梢又在脑干中建立了两条独立的通路。一条路径提取耳间时间差，而另一条路径专门用于处理耳间强度差异。 在接下来的两年中，我们提出了两个具体目标来探索与这些双耳回路相关的兴奋性和抑制性输入的突触组织。我们将使用电子显微镜和免疫细胞化学来表征和量化传入终端，通过比较正常听力猫和有或没有人工耳蜗植入的先天性耳聋猫的数据来测试有关先天性耳聋如何影响双耳回路的具体假设。重点将放在球形丛状细胞及其投射到外侧和内侧上橄榄核的主细胞上，以及投射到梯形体内侧核的主细胞上的球状丛状细胞上。这些目标将评估人工耳蜗刺激对大脑可塑性的影响，并检验某些听觉回路比其他听觉回路更容易恢复的假设。 这项研究利用了一群表现出遗传性耳聋的独特猫群，以及先进仿生公司慷慨赠送的双边人工耳蜗植入物。研究结果将增进我们对人工耳蜗和耳聋对大脑可塑性作用的理解。这些数据还可能有助于解释为什么双侧植入物使用者的耳间水平差异比耳间时间差异更显着。最后，新知识可能有助于改善双侧人工耳蜗使用者的治疗策略，并影响听觉脑干植入的考虑因素。