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 美国七个成年人中有一个在听力方面很难。大多数听力损失与 内耳功能障碍。听力损失的突出签名是外毛细胞的损害，这可能导致 40-60 dB的听力损失。外毛细胞被称为细胞致动器，是人工耳蜗所需的 放大。外毛细胞位于称为Corti器官的人工耳蜗感觉上皮。这 Corti的器官夹在两个称为基底和tecorial的胶原纤维的矩阵之间 膜。传统上，对耳蜗扩增的研究集中在基底膜的运动上， 但是新的证据表明，我们只看到了故事的一面（外部的基础侧 毛细胞）。影像学和速度计技术的最新进步使科学家能够“透明” 耳蜗，以便它们可以捕获基底膜以外的Corti运动器官。使用新观察 最近的技术既令人兴奋又难题。例如，在外毛细胞的顶端 与基底膜运动或神经反应相比，振动是广泛调整的。功能 机械调谐之间不一致的后果尚不清楚。有两个挑战 阻碍了听力科学关于人工耳蜗的进步。首先，最近的进步， 速度测量技术的分辨率不足以指定单个外毛细胞。第二，在 对活动物进行的实验，控制外毛细胞生理的方法非常有限。 该项目解决了这两个挑战。我们已经开发了新颖的体外方法，使我们能够 测量在电，化学和机械控制下单个外毛细胞的运动 状况。我们的虚拟耳蜗解释和扩展了实验结果 - 一组计算机 分析人工耳蜗机械转移的模型。通过结合这些实验和计算机 模型，我们可以确保我们的研究的科学严格性，同时最大程度地减少动物的使用。对于透明，被收购 数据和计算机程序将公开提供。 该提案的三个目标旨在量化所需的最需要的生物物理属性 解决有关人工耳蜗放大和调整的开放问题。它们是1）立体柔性的挠度 （毛细胞的机械受体细胞器）由于外毛细胞运动性，2） Tecorial膜和Deiters细胞（与外毛细胞串联结构），3）操作范围 立体机械转移（立体旋转偏转至饱和毛细胞机械转导的偏转）。这 通过与三个目标的测量值进行比较，在测试我们的总体之前，可以通过与三个目标的测量进行比较来验证虚拟耳蜗 假设 - Corti的器官必须像外毛细胞一样合规，以生成外毛细胞 耳蜗放大的功率。