Experimental - Theoretical Studies of Cochlear Mechanisms

越来越清楚的是，作为标志的非凡的声学灵敏度和频率选择性 我们的听觉来源于微机械机制。基因操作表明， 覆膜（TM）在此过程中起重要作用。但总的来说， 部分原因是缺乏对TM特性的直接测量。我们建议进行研究， 通过三个相关类别的研究了解TM的作用，[a.]我们建议测量 TM的材料特性，以确定其分子基础和功能意义。我们将联合收割机 TM的机械、化学、渗透和电学测量，以表征其材料特性 作为耳蜗中纵向位置的函数。这些材料特性将提供定量的 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 基因突变对TM材料特性的影响。几种人类遗传性听力障碍 来自TM蛋白的突变。来自小鼠模型的TM的材料性质的测量 这些障碍将提供对人类听力障碍的生理基础的更好理解， 并将阐明TM材料特性的分子基础。[c.]我们建议测量 在分离但完整的耳蜗中TM与其他耳蜗结构的耦合。我们将应用 位移的镫骨和测量所产生的运动的TM和头发束的内部和 外毛细胞这些测量将提供直接测试的假设的作用，TM在 耳蜗力学这种知识的实际好处应包括更准确地描述 内耳疾病，治疗建议，假体装置的开发，以及>纳入 将内耳处理的知识引入到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.... :¿¿