Investigation of the role of the tectorial membrane in cochlear mechanics using computational models

项目摘要 转基因小鼠的生理记录和耳声发射（OAE）测量有助于 目的：研究耳蜗盖膜（TM）基因突变对耳蜗功能的影响。然而，在这方面， 目前对TM在哺乳动物听力机制中的作用的理解仍然有限。本研究 旨在阐明TM在听力力学中的作用，使用野生型和 转基因小鼠更具体地说，拟议的研究重点是TM在主动反馈中的作用 一种称为耳蜗放大器的机制，它是实现急剧调谐和高灵敏度所必需的， 低水平的声音。具体目标1旨在确定TM的基因突变如何改变机械耦合 外毛细胞具体目标2将确定转基因材料中TM机械性能的变化 小鼠影响耳蜗调谐和基于OAE的耳蜗调谐测量。具体目标3将调查 增强某些类型的耳声发射的潜在机制，以前曾在一些 转基因小鼠为了实现本研究的目标，我们将仔细模拟 TM的结构、解剖结构和机械性能上的突变，并将预测 通过使用基于生理学的小鼠计算模型， 耳蜗理论模型将使用已发表的实验数据和新的实验数据进行验证， 将由我们的合作者提供。此外，我们将进行理论预测， 由我们的合作者测试。这项研究的结果将证明，我们独特的虚拟实验室， 听力力学包括耳蜗微观力学和TM力学的细节，构成了一个复合体， 可以解释侵入性生理数据以及非侵入性OAE测量的抽象框架。如果 成功，这项研究将有助于更好地诊断和治疗听力障碍和听觉障碍引起的 由于TM中表达的蛋白质的一些突变与TM的遗传异常有关， 人类遗传性耳聋这项研究的结果也将促进助听器的设计， 通过帮助从非侵入性耳声发射测量中提取更多信息来帮助人工耳蜗植入。

PROJECT SUMMARY Physiological recordings and measurements of otoacoustic emissions (OAEs) in transgenic mice have helped to characterize the effects of genetic mutations of the tectorial membrane (TM) on cochlear function. However, current understanding of the role of the TM in mammalian hearing mechanics remains limited. This research aims to elucidate the role of the TM in hearing mechanics using computational models of wild-type and transgenic mice. More specifically, the proposed research focuses on the role of the TM in the active feedback mechanism called cochlear amplifier that is necessary to achieve sharp tuning and high sensitivity in response to low level sounds. Specific Aim 1 seeks to determine how genetic mutations of the TM alter mechanical coupling of outer hair cells. Specific Aim 2 will establish how changes in the mechanical properties of the TM in transgenic mice affect cochlear tuning and OAE-based measures of cochlear tuning. Specific Aim 3 will investigate the underlying mechanism for the enhancement of some types of OAEs that has previously been reported in some transgenic mice. In order to accomplish the objectives of this research, we will carefully model the effects of the mutations on the structure, anatomy, and mechanical properties of the TM and will predict the effect of the mutations on cochlear mechanics and OAEs by using a physiologically-based computational model of the murine cochlea. Theoretical models will be validated using published experimental data and new experimental data that will be provided by our collaborators. Furthermore, we will make theoretical predictions that will be experimentally tested by our collaborators. The results of this research will demonstrate that our unique virtual laboratory for hearing mechanics that includes details about cochlear micromechanics and TM mechanics constitutes a com- prehensive framework that can explain invasive physiological data as well as noninvasive OAE measurements. If successful, this research will help to better diagnose and treat hearing impairment and auditory disorders caused by genetic abnormalities of the TM, since some mutations of the proteins expressed in the TM have been linked to human hereditary deafness. The results of this research will also facilitate the design of hearing aids and cochlear implants by helping to extract more information from noninvasive OAE measurements.