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The Role of the Organ of Corti for Cochlear Power Transmission

柯蒂氏器在耳蜗动力传输中的作用

基本信息

批准号：
10372625
负责人：
Jong-Hoon Nam
金额：
$ 51.36万
依托单位：
UNIVERSITY OF ROCHESTER
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：
2015-06-15 至 2026-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10372625
关键词：
Address Adult Affect Animals Apical Basilar Membrane Biophysics Cell physiology Cells Cellular Structures Chemicals Cochlea Collagen Fiber Complex Computer Models Computer Simulation Custom Data Electric Stimulation Ensure Epithelial Frequencies Functional disorder Hair Cells Hearing Human Image In Situ In Vitro Individual Labyrinth Link Liquid substance Location Measurement Measures Mechanical Stimulation Mechanics Methods Modeling Molecular Motion Optical Coherence Tomography Organ Organ of Corti Organelles Outcome Outer Hair Cell of the Organ of the Corti Outer Hair Cells Physics Play Property Public Health Quality of life Radial Research Resolution Role Science Scientist Sensory Series Side Structure Supporting Cell System Techniques Testing To specify United States Velocimetries biophysical properties cell motility computer program design electric impedance electrical potential experience experimental study hearing impairment improved in vivo mechanical properties mechanotransduction neuronal cell body novel relating to nervous system response sound tectorial membrane theories tool transmission process vibration virtual

项目摘要

Project Summary One out of seven adults in the United States suffers difficulty in hearing. Most hearing loss is related to inner ear dysfunction. A prominent signature of hearing loss is damage of outer hair cells, which can result in 40-60 dB of hearing loss. Outer hair cells are known as cellular actuators that are needed for cochlear amplification. Outer hair cells are situated in the cochlear sensory epithelium called the organ of Corti. The organ of Corti is sandwiched between two collagen-fiber-rich matrices called the basilar and tectorial membranes. Traditionally, studies on cochlear amplification were focused on motion of the basilar membrane, but new evidence is suggesting that we have been seeing only one-side of the story (basal-side of the outer hair cells). Recent advancement in imaging and velocimetry techniques enables scientists to ‘see-through’ the cochlea so that they can capture organ of Corti motion beyond the basilar membrane. New observations using recent techniques are both exciting and puzzling. For example, at the apical side of the outer hair cell, vibrations are broadly tuned as compared to basilar membrane motion or neural responses. Functional consequences of the incongruence between mechanical and neural tuning are unclear. Two challenges are impeding the progress of hearing science regarding cochlear amplification. First, despite recent progress, the resolution of velocity measurement techniques is insufficient to specify individual outer hair cells. Second, in experiments with live animals, there are very limited means to control outer hair cell physiology. This project resolves those two challenges. We have developed novel in vitro methods that enable us to measure the motion of individual outer hair cells under electrically, chemically and mechanically controlled conditions. Experimental outcomes are explained and extended by our Virtual Cochlea—a set of computer models to analyze cochlear mechano-transduction. By combining these experiments and the computer models, we can ensure scientific rigor of our research while minimizing animal use. For transparency, acquired data and computer programs will be made available to public. The three aims of this proposal are designed to quantify the most needed biophysical attributes needed to address open questions regarding cochlear amplification and tuning. They are 1) the deflection of stereocilia (mechano-receptive organelle of the hair cells) due to outer hair cell motility, 2) mechanical properties of the tectorial membrane and the Deiters cell (structures in series with the outer hair cell), and 3) the operating range of stereocilia mechano-transduction (stereocilia deflection to saturate hair cell mechano-transduction). The Virtual Cochlea is validated by comparing with the measurements of three aims before testing our overarching hypothesis—the organ of Corti must be as compliant as the outer hair cells for the outer hair cells to generate power for cochlear amplification.

项目总结