Cochlear mechanics in the mouse

项目总结/摘要 声压在哺乳动物耳蜗分区产生力，最终产生振动 沿耳蜗管纵向传播的行波。这个过程的主要特点是 来自非哺乳动物耳蜗的是放大， （OHC）锐化和放大行波。我们的首要目标是了解复杂的 形成Corti器官的3D多细胞和非细胞排列的生物力学共同作用， 产生耳蜗放大。具体来说，我们将确定这一过程，这源于广泛的- 调谐基底膜，创建尖锐的频率调谐和高灵敏度。这个问题在A 基础科学水平，因为这些生物物理过程的基础是听到声音的能力， 分子在空气中的布朗运动，具有精确的频率分辨率。这个问题仍然没有解决 并且在临床上是重要的，因为听力损失通常是由于耳蜗放大的损失。我们的中央 假设是，除了基底膜力学提供的广泛调谐之外， OHC还通过其他机制进行调整。在目标1中，我们将使用3D体积光学相干 断层扫描和振动测量法（VOCTV）在小鼠中测试OHC产生的力是否由 支持细胞和形成Corti器官的非细胞结构的力学。在目标2中，我们将使用1D 在清醒行为小鼠中的VOCTV，以测试耳蜗放大是否通过 内侧橄榄耳蜗传出（MOC）系统通过不同的OHC力的产生。这些数据将被 来检验我们的假设。如果我们的假设是正确的， Corti器官是产生哺乳动物耳蜗和大脑的灵敏度和敏锐调谐所必需的 状态通过MOC传出系统调节耳蜗放大。

Project Summary/Abstract 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 form 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, beyond the broad tuning provided by basilar membrane mechanics, the forces produced by OHCs are also tuned by additional mechanisms. In aim 1, we will use 3D Volumetric Optical Coherence Tomography and Vibrometry (VOCTV) in mice to test whether the forces produced by OHCs are tuned by the mechanics of the supporting cells and acellular structures that form the organ of Corti. In aim 2, we will use 1D VOCTV in awake behaving mice to test whether cochlear amplification is modulated by brain state via the medial olivocochlear efferent (MOC) system by varying OHC force production. 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 and brain state modulates cochlear amplification via the MOC efferent system.