The Role of the Organ of Corti for Cochlear Power Transmission

柯蒂氏器在耳蜗动力传输中的作用

• 批准号: 10531247
• 负责人: Jong-Hoon Nam
• 金额: $ 43.97万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-15 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10531247
• 关键词: Address; Adult; Affect; Animals; Apical; Basilar Membrane; Biophysics; Cell Communication; Cell physiology; Cells; Chemicals; Cochlea; Collagen Fiber; Complex; Computer Models; Computer Simulation; Data; Electric Stimulation; Ensure; Epithelium; Frequencies; Functional disorder; Hair Cells; Hearing; Human; Image; In Situ; In Vitro; Individual; Labyrinth; Link; Liquid substance; Location; Measurement; Measures; Mechanical Stimulation; Mechanics; Methods; Modeling; Molecular; Motion; Optical Coherence Tomography; Organ; Organ of Corti; Organelles; Outcome; Outer Hair Cells; Physics; Play; Property; Public Health; Quality of life; Radial; Research; Resolution; Role; Science; Scientist; Sensory; Series; Side; Specific qualifier value; Structure; Supporting Cell; System; Techniques; Testing; United States; Velocimetries; biophysical properties; cell motility; computer program; design; electric impedance; electrical potential; experience; experimental study; hearing impairment; improved; in vivo; mechanical properties; mechanotransduction; neural; neuronal cell body; novel; response; sound; tectorial membrane; theories; tool; transmission process; vibration; virtual

Project Summary One out of seven adults in the United States suffers difficulty in hearing. Most hearing loss is related to inner ear dysfunction. A prominent signature of hearing loss is damage of outer hair cells, which can result in 40-60 dB of hearing loss. Outer hair cells are known as cellular actuators that are needed for cochlear amplification. Outer hair cells are situated in the cochlear sensory epithelium called the organ of Corti. The organ of Corti is sandwiched between two collagen-fiber-rich matrices called the basilar and tectorial membranes. Traditionally, studies on cochlear amplification were focused on motion of the basilar membrane, but new evidence is suggesting that we have been seeing only one-side of the story (basal-side of the outer hair cells). Recent advancement in imaging and velocimetry techniques enables scientists to ‘see-through’ the cochlea so that they can capture organ of Corti motion beyond the basilar membrane. New observations using recent techniques are both exciting and puzzling. For example, at the apical side of the outer hair cell, vibrations are broadly tuned as compared to basilar membrane motion or neural responses. Functional consequences of the incongruence between mechanical and neural tuning are unclear. Two challenges are impeding the progress of hearing science regarding cochlear amplification. First, despite recent progress, the resolution of velocity measurement techniques is insufficient to specify individual outer hair cells. Second, in experiments with live animals, there are very limited means to control outer hair cell physiology. This project resolves those two challenges. We have developed novel in vitro methods that enable us to measure the motion of individual outer hair cells under electrically, chemically and mechanically controlled conditions. Experimental outcomes are explained and extended by our Virtual Cochlea—a set of computer models to analyze cochlear mechano-transduction. By combining these experiments and the computer models, we can ensure scientific rigor of our research while minimizing animal use. For transparency, acquired data and computer programs will be made available to public. The three aims of this proposal are designed to quantify the most needed biophysical attributes needed to address open questions regarding cochlear amplification and tuning. They are 1) the deflection of stereocilia (mechano-receptive organelle of the hair cells) due to outer hair cell motility, 2) mechanical properties of the tectorial membrane and the Deiters cell (structures in series with the outer hair cell), and 3) the operating range of stereocilia mechano-transduction (stereocilia deflection to saturate hair cell mechano-transduction). The Virtual Cochlea is validated by comparing with the measurements of three aims before testing our overarching hypothesis—the organ of Corti must be as compliant as the outer hair cells for the outer hair cells to generate power for cochlear amplification.

项目摘要 在美国，每七个成年人中就有一个患有听力障碍。大多数听力损失都与 内耳功能障碍。听力损失的一个显著特征是外毛细胞的损伤，这可能导致 听力损失40-60分贝。外毛细胞是耳蜗所必需的细胞致动器。 放大。外毛细胞位于耳蜗感觉上皮内，称为Corti器官。这个 Corti器官夹在两种富含胶原纤维的基质之间，称为基底膜和覆盖层。 膜。传统上，耳蜗术的研究主要集中在基底膜的运动， 但新的证据表明，我们只看到了故事的一个方面(外部的基础方面 毛细胞)。成像和测速技术的最新进展使科学家们能够“看穿” 这样他们就可以捕捉到基底膜以外的Corti器官的运动。新的观察结果使用 最近的技术既令人兴奋，又令人费解。例如，在外毛细胞的顶端， 与基底膜运动或神经反应相比，振动的调谐范围很广。功能性 机械调谐和神经调谐之间不一致的后果尚不清楚。两个挑战是 阻碍了有关耳蜗术的听力科学的进步。首先，尽管最近取得了进展，但 速度测量技术的分辨率不足以确定单个外毛细胞。第二，在 在活体动物实验中，控制外毛细胞生理学的手段非常有限。 该项目解决了这两个挑战。我们已经开发出新的体外方法，使我们能够 测量单个外毛细胞在电、化学和机械控制下的运动 条件。通过我们的虚拟耳蜗机--一套计算机，解释和扩展了实验结果 分析耳蜗机能传导的模型。通过将这些实验和计算机相结合 有了模型，我们可以确保我们研究的科学严谨性，同时最大限度地减少动物使用。为了提高透明度，收购了 数据和计算机程序将向公众开放。 该提案的三个目标旨在量化最需要的生物物理属性 解决有关耳蜗放大和调谐的公开问题。它们是1)立体纤毛的偏转 (毛细胞的机械感受器)由于外毛细胞的运动，2)机械特性 覆盖膜和Deiters细胞(与外毛细胞串联的结构)，以及3)工作范围 静纤毛机械转导(静纤毛偏转至饱和毛细胞机械转导)。这个 在测试我们的总体结构之前，通过比较三个目标的测量结果来验证虚拟耳蜗器的有效性 假设--Corti的器官必须与外毛细胞一样顺从，才能产生外毛细胞 用于耳蜗放大的功率。