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（由申请人提供）：声压产生穿过哺乳动物耳蜗分区的力，最终产生沿耳蜗管纵向传播的振动行波。这一过程与非哺乳动物耳蜗的主要区别在于放大，数千个外毛细胞（OHC）产生的力使行波变尖并放大。我们的首要目标是了解形成Corti器官的3D多细胞和非细胞排列的复杂生物力学如何共同工作以创建耳蜗放大。具体来说，我们将确定这个过程，这源于广泛调谐的基底膜，创造尖锐的频率调谐和高灵敏度。这个问题在基础科学层面上是重要的，因为这些生物物理过程是以精确的频率分辨率听到空气中分子布朗运动以上的声音的能力的基础。这个问题仍然没有解决，并且在临床上很重要，因为听力损失通常是由于耳蜗放大的损失。我们的中心假设是，Corti器官的机械特性提供了额外的过滤，超出了由基底膜和周围液体的被动力学提供的过滤，并且这调节OHC力的产生，以产生观察到的灵敏度和尖锐的频率调谐。为了验证这一假设，我们开发了一种创新技术，称为体积光学相干断层扫描振动测量（VOCTV）。除了允许传统的在体基底膜运动测量，VOCTV还允许测量整个Corti器官的声致振动。我们建议使用VOCTV来研究Corti器官组成部分之间的相互作用，并评估它们如何与小鼠耳蜗顶转内的耳蜗放大相关。在目标1中，我们首次提出在活体内测量野生型小鼠耳蜗顶圈内的横向和径向振动运动。我们将使用3D定位来比较不同Corti器官结构的响应，评估耳蜗放大的频率响应和增益。在目标2中，我们建议测量几种转基因小鼠品系的顶转内的振动运动，这些转基因小鼠品系具有旨在选择性地改变Corti机械器官的分子变化。通过这种方法，我们将探讨prestin为基础的电运动，立体纤毛束力学，覆膜行波，和毛细胞/支持细胞图案的机械贡献。这些数据将被解释为检验我们的假设。如果我们的假设是正确的，那么Corti器官内尖锐调谐的差动运动对于产生哺乳动物耳蜗的灵敏度和尖锐调谐是必要的。