Experimental - Theoretical Studies of Cochlear Mechanisms

描述（由申请人提供）：基于其战略位置，长期以来被认为在听力中起重要作用，但耳蜗的机制尚不清楚。我们建议研究以提高我们对TM在确定(1)正常听力的显着特性（包括其精湛的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方面的功能作用的理解。拟议的研究分为三个相关的目标。目的1：我们建议测量TM的动态特性，以确定生理上重要特性的分子起源，如剪切刚度和损失模量，电荷密度和相关的电动力学行为，以及TM的行波。目的2：我们建议测量基因操作对TM动态特性的影响。在转基因小鼠中测量TM波、纵向耦合、电荷密度和TM的电动力学将为理解相应听力障碍的物理基础提供一个框架。目的3：我们建议在分离的完整耳蜗中测量TM与其他耳蜗结构的相互作用。我们将测量TM和毛束响应镫骨运动的相对运动。这些测量将提供直接测试TM在刺激毛束和沿耳蜗螺旋传播兴奋方面的作用。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。这些知识对于内耳疾病的描述（以及伴随的治疗建议）和语音处理设备（如人工耳蜗、助听器和语音识别系统）的设计具有重要的实际应用。

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.