The role of the organ of Corti for cochlear power transmission

柯蒂氏器在耳蜗电力传输中的作用

• 批准号: 9270013
• 负责人: Jong-Hoon Nam
• 金额: $ 38.38万
• 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 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9270013
• 关键词: Achievement; Acoustics; Adult; Affect; Biophysics; Cells; Cellular Structures; Chemicals; Clinical; Cochlea; Complex; Computer Simulation; Coupled; Coupling; Custom; Data; Elements; Epithelium; Equilibrium; Extracellular Structure; Financial compensation; Finite Element Analysis; Frequencies; Functional disorder; Generations; Geometry; Goals; Hair Cells; Hearing; In Situ; In Vitro; Inner Hair Cells; Kinetics; Labyrinth; Lasers; Link; Liquid substance; Location; Measurement; Measures; Mechanics; Mediating; Microfluidic Microchips; Microfluidics; Modeling; Molecular; Organ Model; Organ of Corti; Outer Hair Cells; Oval Window; Physics; Physiological; Physiology; Property; Public Health; Radial; Receptor Cell; Research; Research Subjects; Role; Science; Sensorineural Hearing Loss; Sensory; Sensory Receptors; Solid; Source; Stimulus; Structure; Supporting Cell; System; Testing; Theoretical Studies; Time; Tissues; Travel; United States; base; biomechanical model; cell motility; clinically relevant; design; electric impedance; experimental study; hearing impairment; kinematics; mechanotransduction; models and simulation; novel; otoacoustic emission; public health relevance; response; sound; sound frequency; tectorial membrane; theories; transmission process; vibration; viscoelasticity

 DESCRIPTION (provided by applicant): Approximately one out of five adults in the United States has some degree of hearing loss. The most common types of hearing loss is sensorineural (i.e., related to inner ear dysfunction). A prominent signature of the sensorineural hearing loss is damage of outer hair cells, which can result in 40-60 dB of hearing loss. Thus the outer hair cells are central to cochlear amplification. The cochlear amplification is a balancing act between the dissipation of energy during vibrations of cochlear epithelium and the compensation of energy by the outer hair cells. The force generation by the outer hair cells has been a hot topic in hearing research, and there has been great progress on that aspect of cochlear amplification. This project will expand the horizon of hearing research in two ways. First, it will focus on the interactions between the outer hair cells and their supporting cells an tissues. The organ of Corti is a cellular complex that mediates the interaction between outer hair cells and their extra-cellular structures that are responsible for cochlear frequency tuning. Secondly, this project will clarify the balancing act in the cochlea by investigating an underappreciated-but-crucial aspect - the energy dissipation. We have a long-term ambition to explain some hearing abnormalities with the view of an imbalance between dissipation and compensation mechanisms in the organ of Corti. This project will be an essential step toward the goal. The primary hypothesis of the project is that the organ of Corti is a micro-machine that optimizes power transmission from the outer hair cell to the stereociliary bundle of the inner hair cell for sound amplification and frequency selectivity. To test this hypothesis, three specific aim were established: 1) to identify the mechanical contribution of the tectorial membrane - an extra-cellular structure overlying the outer hair cells, 2) to examine the source and role of resistive damping in the organ of Corti, and 3) to examine the power flux due to outer hair cell motility. This project uses a detailed computational model of the organ of Corti and a novel experimental approach to observe the multi-cellular physics of the organ of Corti complex. The computational model is focused on the interactions between active outer hair cells and their surrounding micro-structures. This project will take full advantage of existing achievements of macro cochlear biophysics by coupling cochlear fluid dynamics with multi-cellular biophysics of the organ of Corti. The experimental approach will facilitate the computational model to draw more concrete conclusions about cochlear power transmission. A novel micro-fluidic chamber system will allow us to control the mechanical, chemical and electrical conditions of the organ of Corti. The results of this project will explain how acoustic energy dissipates in the organ of Corti. A clinically relevant example of the imbalance between dissipation and compensation will be investigated - the spontaneous otoacoustic emission.

 描述（由适用提供）：在美国，大约有五分之一的成年人有一定程度的听力损失。听力损失的最常见类型是感觉神经性（即与内耳功能障碍有关）。感官听力损失的明显标志是外毛细胞的损害，这可能导致40-60 dB的听力损失。外毛细胞是人工耳蜗放大的核心。人工耳蜗放大是在人工耳蜗上皮振动期间能量耗散与外毛细胞对能量补偿的平衡行为。外毛细胞的力量产生一直是听力研究的热门话题，在耳蜗放大方面取得了长足的进步。该项目将通过两种方式扩大听力研究的视野。首先，它将集中于外毛细胞与其支持细胞之间的相互作用。 Corti的器官是一种细胞复合物，可介导外毛细胞与其细胞外结构之间的相互作用，该结构负责耳蜗频率调整。其次，该项目将通过调查未充分利用但至关重要的方面 - 能量耗散来阐明耳蜗中的平衡法。我们有一个长期的野心来解释一些听力异常，以表明Corti器官中耗散和补偿机制之间的不平衡。该项目将是朝着目标迈出的重要一步。该项目的主要假设是Corti的器官是一种微动机，可优化从外毛细胞到内发的立体束的动力传输 用于声音扩增和频率选择性的单元格。为了检验这一假设，建立了三个特定的目的：1）确定技术膜的机械贡献 - 外毛细胞上覆盖的细胞外结构，2）检查电阻阻尼在Corti器官中的来源和作用，以及3）检查由于外毛细胞的动力通量而导致的功率通量。该项目使用Corti器官的详细计算模型和一种新型的实验方法来观察Corti复合物器官的多细胞物理学。计算模型集中在活动的外毛细胞及其周围微结构之间的相互作用上。该项目将通过将耳蜗液体动力学与Corti器官的多细胞生物物理学耦合，从而充分利用了现有的宏耳蜗生物物理学的成就。实验方法将准备计算模型，以得出有关耳蜗功率传播的更具体结论。一种新型的微氟腔室系统将使我们能够控制Corti器官的机械，化学和电气条件。结果 该项目将解释声能在Corti器官中消散。将研究耗散和补偿之间的不平衡的临床相关例子 - 赞助商 - 客观的耳声发射。