Experimental_Theoretical_Studies_of_Cochlear_Mechanisms

摘要 基于其战略位置，覆膜（TM）长期以来一直被认为在以下方面发挥重要作用： 听力，但重要的耳蜗机制仍不清楚。我们建议进行研究， TM在确定（1）正常听力的显着特性-包括其 灵敏度和频率选择性-以及（2）与基因突变相关的听力损失， TM和其他耳蜗病变。拟议的研究有三个相关的目标。目标1：我们 建议表征TM材料特性，这些特性决定TM、发束 和周围的水。我们将测量TM的多孔弹性和电动力学特性， 在微米和纳米尺度上的毛束。目的2：我们提出测量TM的径向和横向模式 刺激内外毛细胞运动的运动。最近的研究挑战了传统的观念 毛束运动完全是由TM（和盖层下的神经胶质）相对于 到网状层除了径向运动模式（例如，共振模型）， TM运动的横向和径向模式被认为是重要的，特别是对于低频刺激， 内毛细胞目标3：我们建议与小鼠相比，表征人类的TM行波和调谐， 沙鼠和豚鼠。虽然哺乳动物耳蜗的横截面结构在物种间高度保守， 听觉的灵敏度和频率选择性大大提高。最近，Tectb-/-中的急剧频率调谐 相对于野生型小鼠的突变小鼠与通过TM行波的纵向耦合中的二聚体有关。 我们建议测试的一般性之间的关系，波的性质和调谐哺乳动物物种， 包括人类我们将测量TM材料特性（例如，剪切刚度和粘性模量）、形态学 (e.g.,径向纤维的宽度、厚度、数量和方向）和小鼠、沙鼠、豚鼠的TM波特性 猪和人类。这三个目标的结果将增加我们对耳蜗机制的理解， 是正常和异常听力的基础这一知识对于划定 内耳疾病（以及伴随的治疗建议）和语音处理设备的设计 例如耳蜗植入物、助听器和语音识别系统。

Abstract Based on its strategic location, the tectorial membrane (TM) has long been believed to play an essential role in hearing, but the important cochlear mechanisms remain unclear. We propose research to improve our understanding of the functional role of the TM in determining (1) the remarkable properties of normal hearing — including its exquisite sensitivity and frequency selectivity — as well as (2) the hearing loss associated with genetic mutations of the TM and other cochlear pathologies. The proposed research is organized with three related aims. Aim 1: We propose to characterize TM material properties that determine local interactions between the TM, hair bundles, and surrounding fluid. We will measure the poroelastic and electrokinetic properties of the TM that interact with the hair bundles at micro- and nano-scales. Aim 2: We propose to measure radial and transverse modes of TM motion that stimulate motions of inner and outer hair cells. Recent studies have challenged the conventional notion that hair bundle motions are generated exclusively by shearing motions of the TM (and subtectorial fluid) relative to the reticular lamina. In addition to radial modes of motion (e.g., resonance models), complex linkages between transverse and radial modes of TM motion are thought to be significant, especially for low-frequency stimulation of inner hair cells. Aim 3: We propose to characterize TM traveling waves and tuning in humans compared to mice, gerbils and guinea pigs. While the cross-sectional structure of the mammal cochlea is highly conserved across species, the sensitivity and frequency selectivity of hearing differs greatly. Recently, the sharp frequency tuning in Tectb-/- mutant mice relative to wild-type mice has been linked to differences in longitudinal coupling via TM traveling waves. We propose to test the generality of the relation between wave properties and tuning across mammalian species, including humans. We will measure TM material properties (e.g., shearing stiffness and viscous moduli), morphology (e.g., width, thickness, number and orientation of radial fibers), and TM wave properties in mice, gerbils, guinea pigs, and humans. Results from these three aims will increase our understanding of the cochlear mechanisms that underlie both normal and abnormal hearing. This knowledge has important practical applications for the delineation of inner-ear disorders (and concomitant suggestions for treatment) and for the design of speech-processing devices such as cochlear implants, hearing aids, and speech-recognition systems.