Cochlear mechanics in the mouse

项目摘要/摘要 声压通过哺乳动物的耳蜗区产生力量，最终产生一种振动 沿耳蜗管纵向传播的行波。区别这一过程的关键特征是 来自非哺乳动物耳蜗的是放大，由数千个外毛细胞产生的力 (OHC)锐化和放大行波。我们的首要目标是了解这个建筑群是如何 形成Corti器官的3D多细胞和无细胞排列的生物力学共同作用于 创建耳蜗放大功能。具体地说，我们将确定这一过程是如何产生的-- 调谐的基底膜，创造了尖锐的频率调谐和高灵敏度。这个问题在一个 基础科学水平，因为这些生物物理过程是听到声音的能力的基础 空气中分子的布朗运动，具有精确的频率分辨率。这个问题还没有解决。 在临床上很重要，因为听力损失通常是由于耳蜗放大能力的丧失。我们的中央 假设是，除了基底膜力学提供的广泛调谐之外，由 OHC还可以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 在小鼠身上进行断层扫描和振动测量(VOCTV)，以测试OHC产生的力是否受到 构成Corti器官的支持细胞和无细胞结构的力学。在目标2中，我们将使用1D VOCTV在清醒行为小鼠中测试耳蜗放大是否受到大脑状态的调节 不同OHC力产生的内侧橄榄耳蜗传出系统(MOC)。加在一起，这些数据将是 以此来验证我们的假设。如果我们的假设是真的，那么 Corti器官是哺乳动物耳蜗和大脑产生敏感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.