Cochlear mechanics in the mouse

小鼠的耳蜗力学

• 批准号: 8859866
• 负责人: John S Oghalai
• 金额: $ 34.68万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8859866
• 关键词: Affect; Air; Apical; Auditory; Autopsy; Basic Science; Basilar Membrane; Biomechanics; Biophysical Process; Characteristics; Cochlea; Cochlear duct; Complex; Data; Frequencies; Hair Cells; Hearing; Hearing Aids; Image; Length; Life; Liquid substance; Literature; Mammals; Measurement; Measures; Mechanics; Molecular; Motion; Mouse Strains; Mus; Mutant Strains Mice; Mutate; Mutation; Optical Coherence Tomography; Organ of Corti; Outer Hair Cells; Pattern; Play; Process; Production; Property; Proteins; Radial; Resolution; Role; Short Waves; Structure; Supporting Cell; Testing; Time; Tissues; Transgenic Mice; Transgenic Organisms; Travel; Ultrasonography; Wild Type Mouse; Work; base; bone; capsule; design; hearing impairment; in vivo; innovative technologies; pressure; public health relevance; rat Pres protein; response; sound; stem; tectorial membrane; vibration

 DESCRIPTION (provided by applicant): Sound pressure produces force across the mammalian cochlear partition, ultimately creating a vibratory traveling wave that propagates longitudinally up the cochlear duct. The key feature distinguishing this process from the non-mammalian cochlea is amplification, whereby forces produced by thousands of outer hair cells (OHCs) sharpen and amplify the traveling wave. Our overarching objective is to understand how the complex biomechanics of the 3D multi-cellular and acellular arrangement that forms the organ of Corti work together to create cochlear amplification. Specifically, we will determine how this process, which stems from the broadly- tuned basilar membrane, creates sharp frequency tuning and high sensitivity. This question is significant on a basic science level because these biophysical processes underlie the ability to hear sounds just above the Brownian motion of molecules in air with an exquisite frequency resolution. This question remains unsolved and is clinically important because hearing loss is typically due to loss of cochlear amplification. Our central hypothesis is that the mechanical properties of the organ of Corti provide additional filtering beyond that provided by the passive mechanics of the basilar membrane and surrounding fluid, and that this modulates OHC force production to give rise to the observed sensitivity and sharp frequency tuning. To test the hypothesis, we have developed an innovative technology, termed Volumetric Optical Coherence Tomography Vibrometry (VOCTV). Besides permitting traditional basilar membrane motion measurements in vivo, VOCTV also permits the measurement of sound-induced vibrations throughout the organ of Corti. We propose to use VOCTV to study the interactions between components of the organ of Corti and assess how they relate to cochlear amplification within the apical turn of the mouse cochlea. In Aim 1, we propose to measure transverse and radial vibratory motions within the apical turn of the wild- type mouse cochlea in vivo for the first time. We will use 3D localization to compare the responses of different organ of Corti structures, assessing both the frequency response and the gain of cochlear amplification. In Aim 2, we propose to measure vibratory motions within the apical turn of several transgenic mouse strains that have molecular changes designed to selectively alter of organ of Corti mechanics. Through this approach, we will probe the mechanical contributions of prestin-based electromotility, stereociliary bundle mechanics, tectorial membrane traveling waves, and hair cell/supporting cell patterning. Together, these data will be interpreted so as to test our hypothesis. If our hypothesis is true, sharply-tuned differential motion within the organ of Corti is necessary to generate the sensitivity and sharp tuning of the mammalian cochlea.

 描述（由适用提供）：声压在哺乳动物的耳蜗分区上产生力，最终形成了振动行动波，该波动波在人工耳蜗上纵向传播。区分这一过程与非哺乳动物人工耳蜗的关键特征是放大，从而由数千个外毛细胞（OHC）产生的力锐化并扩大了行驶波。我们的总体目标是了解3D多细胞和细胞排列的复杂生物力学如何形成Corti的器官，共同创建耳蜗扩增。具体而言，我们将确定该过程是如何从广泛调整的基底膜中植物产生尖锐的频率调整和高灵敏度的。这个问题在基础科学水平上很重要，因为这些生物物理过程的基础是在空气中以精美的频率分辨率在空气中的布朗分子运动之上听起来的能力。这个问题仍未解决，并且在临床上很重要，因为听力损失通常是由于人工耳蜗放大的丧失。我们的中心假设是，Corti器官的机械性能提供了额外的过滤，而不是基底膜和周围流体的被动机制提供的额外过滤，并且该调节OHC力的产生使观察到的敏感性和清晰的频率调谐产生。为了检验该假设，我们开发了一种创新技术，称为体积光学相干断层扫描（VOCTV）。除了允许在体内进行传统的基底膜运动测量外，VOCTV还允许在整个Corti器官中测量声诱导的振动。我们建议使用VOCTV研究Corti器官器官的组件之间的相互作用，并评估它们与AIM 1中顶端内的人工耳蜗扩增之间的关系，我们建议在VIVO中野生型小鼠Cochlea的顶端测量横向和径向振动运动。我们将使用3D定位比较皮质结构的不同器官的响应，从而评估耳蜗放大的频率响应和增益。在AIM 2中，我们建议在几个具有分子变化的转基因菌株的顶部转弯内测量振动动作，这些转换旨在选择性地改变Corti机械器官。通过这种方法，我们将探测基于Prestin的电力，立体束机械，Tectorial Membrane行进波以及毛细胞/支撑细胞模式的机械贡献。共同解释这些数据以检验我们的假设。如果我们的假设是真实的，则必须在Corti器官内部较明确调节的差分运动，以产生哺乳动物耳蜗的灵敏度和尖锐的调整。