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

项目总结 转基因小鼠的生理记录和耳声发射(OAEs)测量有所帮助 目的：研究覆膜(TM)基因突变对耳蜗功能的影响。然而， 目前对TM在哺乳动物听力机制中的作用的了解仍然有限。这项研究 目的是利用Wildtype和Wildtype的计算模型来阐明TM在听力力学中的作用 转基因小鼠。更具体地说，提出的研究侧重于TM在主动反馈中的作用 称为耳蜗放大器fier的机制，是实现尖锐调谐和高灵敏度响应所必需的 很低的声音。SPECIfic Aim 1试图确定TM的基因突变如何改变机械耦合 外毛细胞。Speific Aim 2将确定转基因TM的机械性能是如何变化的 老鼠会影响耳蜗调优和基于耳声发射的耳蜗调优措施。Speific Aim 3将调查 一些先前报道的增强某些类型的OAE的潜在机制 转基因小鼠。为了实现这项研究的目标，我们将仔细模拟 突变对TM的结构、解剖和机械性能的影响，并将预测 利用基于生理学的小鼠计算模型研究耳蜗力学和耳声发射的突变 耳蜗骨。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，我们将做出理论预测，这些预测将在实验中进行。 经过我们的合作者测试。这项研究的结果将证明我们独特的虚拟实验室 听力力学包括有关耳蜗细观力学和TM力学的细节，构成了一个组件。 全面的框架，可以解释侵入性生理数据以及非侵入性耳声发射测量。如果 这项研究的成功将有助于更好地诊断和治疗听力障碍和听力障碍引起的 由于TM的遗传异常，因为TM中表达的蛋白质的一些突变被联系在一起 人类遗传性耳聋。这项研究的结果也将有助于助听器的设计和 通过帮助从非侵入性耳声发射测量中提取更多信息，我们可以为人工耳蜗植入物提供更多信息。

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.