Experimental - Theoretical Studies of Cochlear Mechanisms

越来越清楚的是，作为标志的非凡的声学敏感性和频率选择性 我们的听觉产生于微机械机制。基因操作表明， 覆膜在这一过程中起着至关重要的作用。但总的来说，这一角色仍然是个谜。 部分原因是缺乏对TM属性的直接测量。我们建议进行研究，以改善我们的 通过对三个相关类别的研究了解商标的作用，[a.]我们建议测量 TM的物质性质决定了它们的分子基础和功能意义。我们将联合起来 对TM进行机械、化学、渗透和电学测量，以表征其材料特性 作为耳蜗轴向位置的函数。这些材料特性将提供一种量化的 理解TM在正常听力中的功能作用的基础，[b]我们建议衡量影响 TM材料特性的基因突变。几种人类遗传性听力障碍 来自TM蛋白的突变。TMS材料特性的小鼠模型测量 这些障碍将提供对人类听力障碍的物理基础的更好理解， 并将阐明TM材料特性的分子基础。[c.]我们建议测量 在一个孤立但完整的耳蜗中，TM与其他耳蜗结构的耦合。我们会申请 并测量胫骨内侧和外侧发束的运动。 外毛细胞。这些测量将直接测试关于TM在 耳蜗机修工。这种知识的实际好处应该包括更准确地描述 内耳疾病，治疗建议，假体设备的开发，以及&gt；合并 将内耳处理知识带入语音处理系统的设计中。：？？

It is increasingly clear that the extraordinary acoustical sensitivity and frequency selectivity that are hallmarks of our sense of hearing arise from micromechanical mechanisms. Genetic manipulations have shown that the tectorial membrane (TM) plays an essential role in this process. But that role remains enigmatic, in large part because of the paucity of direct measurements of TM properties. We propose research to improve our understanding of the role of the TM with studies in three related categories, [a.] We propose to measure material properties of the TM to determine their molecular basis and functional significance. We will combine mechanical, chemical, osmotic and electrical measurements of the TM to characterize its material properties as a function of longitudinal position in the cochlea. These material properties will provide a quantitative basis for understanding the functional role of the TM in normal hearing, [b.] We propose to measure effects of genetic mutations on material properties of the TM. Several human genetic disorders of hearing result from mutations of TM proteins. Measurements of the material properties of TMs from mouse models of these disorders will provide a better understanding of the physical basis of the human disorders of hearing, and will elucidate the molecular basis of the material properties of the TM. [c.] We propose to measure coupling of the TM to other cochlear structures in an isolated, but intact cochlea. We will apply displacements to the stapes and measure the resulting motions of the TM and hair bundles of inner and outer hair cells. These measurements will provide direct tests of hypotheses about the role of the TM in cochlear mechanics. The practical benefits of this knowledge should include more precise delineation of inner ear disorders, suggestions for treatment, development of prosthetic devices, and>incorporation of knowledge of inner-ear processing into the design of systems for processing speech.... :¿¿