Cochlear mechanics in the mouse

小鼠的耳蜗力学

基本信息

批准号：
10394238
负责人：
John S Oghalai
金额：
$ 62.33万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10394238
关键词：
3-Dimensional Affect Air Anatomy Anesthesia procedures Animals Arousal Auditory Auditory system Back Basic Science Basilar Membrane Biomechanics Biomedical Engineering Biophysical Process Brain Caliber Characteristics Clinical Cochlea Cochlear duct Complex Data Dependence Environment External auditory canal Frequencies Hair Cells Head Hearing Hearing Aids Image Left Mammals Measurement Measures Mechanics Medial Mediating Motion Mus Optical Coherence Tomography Optics Organ of Corti Outer Hair Cells Painless Physiology Process Production Pupil Reflex action Research Project Grants Resolution Role Speech Structure Supporting Cell System Technology Testing Time Travel Walking Wild Type Mouse Work auditory stimulus awake bone capsule design experimental study hearing impairment in vivo indexing innovation otoacoustic emission peer pressure response sound stem tectorial membrane treadmill vector vibration walking speed

项目摘要

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.

项目概要/摘要声压产生穿过哺乳动物耳蜗分区的力，最终产生振动沿耳蜗管纵向传播的行波。区分此过程的关键特征来自非哺乳动物耳蜗的放大作用是由数千个外毛细胞产生的力 (OHC) 锐化并放大行波。我们的首要目标是了解复杂的构成柯蒂氏器官的 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，我们将确定这个过程如何产生，它源于广泛的- 调谐基底膜，产生尖锐的频率调谐和高灵敏度。这个问题对于一个人来说很重要基础科学水平，因为这些生物物理过程是听到略高于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。这个问题仍然悬而未决这在临床上很重要，因为听力损失通常是由于耳蜗放大功能丧失所致。我们的中央假设是，除了基底膜力学提供的广泛调节之外，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中进行断层扫描和振动测量 (VOCTV)，以测试 OHC 产生的力是否由形成柯蒂氏器的支持细胞和非细胞结构的力学。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通过大脑状态调节内侧橄榄耳蜗传出 (MOC) 系统通过不同的 OHC 力产生。这些数据一起将解释以检验我们的假设。如果我们的假设成立，那么在柯蒂氏器对于哺乳动物耳蜗和大脑的敏感性和敏锐调节是必需的状态通过 MOC 传出系统调节耳蜗放大。