The role of the organ of Corti for cochlear power transmission

 描述（由申请人提供）：在美国，大约五分之一的成年人有一定程度的听力损失。最常见的听力损失类型是感觉神经性（即，与内耳功能障碍有关）。感音神经性听力损失的一个突出特征是外毛细胞的损伤，这可能导致40-60 dB的听力损失。因此，外毛细胞是耳蜗放大的中心。耳蜗放大是耳蜗上皮细胞振动过程中能量耗散与外毛细胞能量补偿之间的平衡作用。耳蜗外毛细胞产生的力一直是听觉研究的热点，耳蜗放大的研究也取得了很大进展。本项目将从两个方面拓展听力研究的视野。首先，它将集中在外毛细胞和它们的支持细胞和组织之间的相互作用。Corti器官是一种细胞复合体，介导外毛细胞与负责耳蜗频率调谐的细胞外结构之间的相互作用。其次，本项目将通过研究一个被低估但至关重要的方面-能量耗散来阐明耳蜗中的平衡行为。我们有一个长期的野心，解释一些听力异常的观点之间的不平衡的耗散和补偿机制的Corti器官。该项目将是实现这一目标的重要一步。该项目的首要假设是，Corti器官是一个微型机器，可以优化从外毛细胞到内毛的静纤毛束的动力传输 用于声音放大和频率选择的细胞。为了验证这一假设，建立了三个具体的目标：1）确定覆膜的机械贡献-覆盖外毛细胞的细胞外结构，2）检查Corti器官中电阻阻尼的来源和作用，以及3）检查由于外毛细胞运动性引起的功率通量。该项目使用Corti器官的详细计算模型和新颖的实验方法来观察Corti器官复合体的多细胞物理学。计算模型的重点是活跃的外毛细胞和它们周围的微结构之间的相互作用。本项目将充分利用宏观耳蜗生物物理学的现有成果，将耳蜗流体动力学与Corti器官的多细胞生物物理学相结合。实验方法将有助于计算模型得出更具体的结论耳蜗功率传输。一种新型的微流体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 这个项目的一部分将解释声能如何在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的例子-自发耳声发射。

 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.