The role of the organ of Corti for cochlear power transmission

 描述(申请人提供)：在美国，大约五分之一的成年人有不同程度的听力损失。最常见的听力损失类型是感觉神经性听力损失(即与内耳功能障碍有关)。感觉神经性听力损失的一个显著特征是外毛细胞受损，可导致40-60分贝的听力损失。因此，外毛细胞是耳蜗放大的中心。耳蜗放大是在耳蜗管上皮细胞振动时能量的耗散和外毛细胞对能量的补偿之间的平衡行为。外毛细胞的作用力一直是听力研究的热点，在耳蜗声放大方面也取得了很大的进展。该项目将从两个方面拓展听力研究的视野。首先，它将关注外毛细胞与其支持细胞和组织之间的相互作用。Corti器官是一个细胞复合体，它调节外毛细胞与其负责耳蜗频率调谐的细胞外结构之间的相互作用。其次，这个项目将通过研究一个未得到重视但却至关重要的方面--能量消耗--来阐明耳蜗中的平衡行为。我们有一个长期的抱负，想用Corti器官的耗散和补偿机制之间的不平衡来解释一些听力异常。这个项目将是迈向这一目标的重要一步。该项目的主要假设是，Corti的器官是一个微型机器，它优化了从外毛细胞到内毛立体纤毛束的能量传递 用于声音放大和频率选择的单元。为了验证这一假说，建立了三个特定的目标：1)确定覆盖膜--覆盖在外毛细胞上的一种细胞外结构--的机械贡献；2)研究Corti器官中阻性阻尼的来源和作用；3)研究外毛细胞运动所产生的能量通量。这个项目使用了一个详细的Corti器官的计算模型和一种新的实验方法来观察Corti复合体器官的多细胞物理。计算模型侧重于活跃的外毛细胞与其周围微结构之间的相互作用。该项目将充分利用已有的宏观耳蜗生物物理学成果，将耳蜗液动力学与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关于耳蜗电传递的结论。一种新颖的微流体室系统将使我们能够控制科尔蒂器官的机械、化学和电气条件。结果是 将解释声能是如何在Corti器官中消散的。一个临床相关的例子，耗散和补偿之间的不平衡将被调查-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.