Experimental - Theoretical Studies of Cochlear Mechanisms

描述（由申请人提供）：基于其战略位置，长期以来一直认为盖膜（TM）在听力中发挥重要作用，但耳蜗机制仍不清楚。我们建议进行研究，以提高我们对TM功能作用的理解，以确定（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TM基因突变和其他耳蜗病变相关的听力损失。拟议的研究分为三个相关的目标。目标1：我们建议测量的TM的动态特性，以确定分子起源的生理上重要的属性，如剪切刚度和损耗模量，电荷密度和相关的电动行为，和行波的TM。目的2：我们建议测量基因操作对TM动力学特性的影响。对转基因小鼠的TM波、纵向耦合、电荷密度和电动力学的测量将为理解相应听力障碍的物理基础提供一个框架。目标3：我们建议在隔离、完整的耳蜗中测量TM与其他耳蜗结构的相互作用。我们将测量相对运动的TM和头发束在镫骨运动的反应。这些测量将提供直接测试TM在刺激毛束和沿耳蜗螺旋沿着传播兴奋中的作用。这三个目标的结果将增加我们对正常和异常听力背后的耳蜗机制的理解。这方面的知识有重要的实际应用内耳疾病的划定（和伴随的治疗建议）和设计的语音处理设备，如人工耳蜗，助听器和语音识别系统。 公共卫生相关性：我们相互交流和在声学丰富的环境中导航的能力取决于内耳对声音的检测和分析。遗传学研究表明，盖膜在这一分析中起着关键作用，但对潜在的机制知之甚少。阐明这些机制的拟议研究将提高我们对正常和受损听力的理解，并对设计语音处理设备（如人工耳蜗、助听器、语音通信和语音识别系统）具有重要意义。

DESCRIPTION (provided by applicant): Based on its strategic location, the tectorial membrane (TM) has long been believed to play an essential role in hearing, but the 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 in three related aims. Aim 1: We propose to measure dynamic properties of the TM to determine the molecular origin of physiologically important properties such as shearing stiffness and loss moduli, charge density and associated electrokinetic behaviors, and traveling waves of the TM. Aim 2: We propose to measure the effects of genetic manipulations on TM dynamic properties. Measurement of TM waves, longitudinal coupling, charge density and electrokinetics of TMs in genetically modified mice will provide a framework for understanding the physical basis of the corresponding hearing disorders. Aim 3: We propose to measure interactions of the TM with other cochlear structures in an isolated, intact cochlea. We will measure relative motions of the TM and hair bundles in response to stapes motion. These measurements will provide direct tests of the TM's role in stimulating the hair bundles and spreading excitation along the cochlear spiral. 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. PUBLIC HEALTH RELEVANCE: Our ability to communicate with each other and to navigate through acoustically rich environments depends on the detection and analysis of sounds by the inner ear. Genetic studies have shown that the tectorial membrane plays a key role in this analysis, but little is known about the underlying mechanisms. The proposed research to clarify these mechanisms will improve our understanding of both normal and impaired hearing and will be important for the design of speech-processing devices such as cochlear implants, hearing aids, and speech-communication and speech-recognition systems.