Experimental - Theoretical Studies of Cochlear Mechanisms

描述（由申请人提供）：越来越清楚的是，非凡的声学灵敏度和频率选择性是我们听觉的标志，它们来自微观力学机制。遗传操作表明，被膜（TM）在这一过程中起着至关重要的作用。但这个角色仍然是个谜，很大程度上是因为缺乏对TM性质的直接测量。我们建议通过3个相关类别的研究来提高我们对TM作用的理解，[a]。我们建议通过测量TM的材料特性来确定其分子基础和功能意义。我们将结合TM的机械，化学，渗透和电学测量来表征其材料特性作为耳蜗纵向位置的函数。这些材料特性将为理解TM在正常听力中的功能作用提供定量基础[b]。我们建议测量基因突变对TM材料性能的影响。几种人类遗传性听力疾病是由TM蛋白突变引起的。从这些障碍的小鼠模型中测量颞叶材料特性将更好地了解人类听力障碍的物理基础，并将阐明颞叶材料特性的分子基础。[c。我们建议在分离但完整的耳蜗中测量TM与其他耳蜗结构的耦合。我们将对镫骨施加位移，并测量由此产生的TM和内部和外部毛细胞的毛束的运动。这些测量将提供直接测试关于TM在耳蜗力学中的作用的假设。这些知识的实际益处应该包括更精确地描述内耳疾病，建议治疗，开发假体装置，以及将内耳处理知识纳入语音处理系统的设计中。

DESCRIPTION (provided by applicant): 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 3 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.