Experimental Theoretical Studies of Cochlear Mechanisms

项目摘要 基于其战略位置，覆盖膜(TM)长期以来一直被认为在 听力，但重要的耳蜗机制仍不清楚。我们建议进行研究以提高我们的理解 TM在确定(1)正常听力的显著特性--包括其 极高的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和其他耳聋的病理改变。传统的耳蜗力学模型将TM表示为一种 粘弹性固体，虽然粘性和弹性的重要性得到了很好的证实，但这些模型并没有 说明了水在这个组织中的中心作用。TM是一种凝胶：97%的水包含在大分子基质中 蛋白质和糖基。最近的研究表明，声音诱导水通过这种大分子的运动 矩阵在确定机械反应的时间上起着关键的作用--而这个时间是中心 以确定频率选择性，这是哺乳动物听力的标志。 拟议的研究将测量和表征胶状性质的重要后果 Tm，即其孔弹性质。这项工作有两个相互关联的目标。fi第一次调查机械 孔洞弹性的后果。我们开发了一种基于原子力显微镜的技术来测量 TM在单发束水平上的力学性能。我们将应用这一技术来表征 听力正常的啮齿动物以及遗传性听力障碍小鼠的TMS的孔弹性。我们的第二个 目的重点研究在TM的液相中溶解的离子(特别是钙)的作用。TM拥有 钙的浓缩程度远远超过周围内淋巴中的钙含量。离子的变化 浓度已被证明可以改变TM的机电性能，从而也将改变ff等 毛细胞紧密相对的发束。ff等人不仅知道局部的钙浓度 声音诱导毛细胞的感受器潜力，也是维持毛细胞 听力异常灵敏。 这些研究的结果将增加我们对耳蜗机制的理解，这些机制是正常和 听力受损。这一知识对于描述内耳疾病(和 随之而来的治疗建议)以及语音处理设备的设计， 助听器和语音识别系统。

Project Summary Based on its strategic location, the tectorial membrane (TM) has long been thought 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. Conventional models of cochlear mechanics represent the TM as a viscoelastic solid, and while the importance of both viscosity and elasticity is well established, these models do not account for the central role of water in this tissue. The TM is a gel: 97% water contained in a macromolecular matrix of proteins and sugar groups. Recent studies show that sound-induced motions of water through this macromolecular matrix plays a critical functional role in determining the timing of mechanical responses – and this timing is central to determining the frequency selectivity that is a hallmark of mammalian hearing. The proposed research will measure and characterize the important consequences of the gelatinous nature of the TM, i.e., its poroelastic properties. This work is organized in two related aims. The first investigates mechanical consequences of poroelasticity. We have developed a technique based on atomic force microscopy to measure mechanical properties of the TM at the level of single hair bundles. We will apply this technique to characterize poroelasticity in TMs from normal-hearing rodents, as well as mice with genetic disorders of hearing. Our second aim focuses on the role of ions (especially calcium) that are dissolved in the liquid phase of the TM. The TM has been shown to concentrate calcium at levels well in excess of those in the surrounding endolymph. Changes in ionic concentrations have been shown to alter the electro-mechanical properties of the TM, and will thereby also affect the closely apposed hair bundles of hair cells. The local concentration of calcium is known to affect not only the sound-induced receptor potentials of hair cells, but also adaptation processes that are necessary to maintain the remarkable sensitivity of hearing. Results from these studies will increase our understanding of the cochlear mechanisms that underlie both normal and impaired 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.