Intracochlear measures of active cochlear mechanics

主动耳蜗力学的耳蜗内测量

• 批准号: 7993087
• 负责人: ELIZABETH S. OLSON
• 金额: $ 19.48万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7993087
• 关键词: Abbreviations; Acoustic Nerve; Acoustic Stimulation; Acoustics; Action Potentials; Aging; Amplifiers; Anatomy; Applications Grants; Auditory; Basilar Membrane; Cellular Structures; Cochlea; Complex; Data; Ear; Electric Stimulation; Elements; Foundations; Frequencies; Future; Genetic Engineering; Gerbils; Hearing; Labyrinth; Learning; Location; Measurement; Measures; Mechanics; Modification; Motion; Mus; Muscle Cramp; Organ of Corti; Outer Hair Cells; Play; Process; Research; Research Project Grants; Role; Scala Tympani; Solutions; Techniques; Terminology; Tympanic membrane; Work; chemotherapy; hearing impairment; in vivo; interest; mouse model; pressure; public health relevance; repaired; response; round window; sound; success

DESCRIPTION (provided by applicant): Two fundamental facts of mammalian auditory processing are: (1) the frequency selectivity that exists in the auditory nerve is due to mechanical preprocessing in the cochlea and (2) the mechanics of the cochlea are highly nonlinear. Cochlear nonlinearity works to boost the mechanical response at low sound pressure levels at frequencies close to the location's best frequency. Thus, cochlear nonlinearity is central to the cochlea's frequency selectivity. In ears in which the mechanics are damaged (through overstimulation, some chemotherapies, and simply aging) nonlinearity is reduced or eliminated, leading to severe loss of hearing acuity. Much remains to be learned about the micromechanical actions and interactions that produce cochlear nonlinearity, termed the "cochlear amplifier." Mouse models in which cellular and acellular cochlear components are altered through genetic engineering have been developed and are already being used to advance our understanding of cochlear mechanics. However, historically mice were not used for cochlear mechanics and robust normative data is lacking. We propose to measure normal intracochlear pressures and motions in mice upon acoustic stimulation. These are the basic responses to normal stimulation. We will also measure pressures and motions upon electrical current stimulation, which is similar and in some ways complementary to acoustic stimulation, and has been used already in modified mouse studies with interesting results. Upon establishing robust normative results we plan to go on, in future projects, to study mice with genetically modified cochlear components. PUBLIC HEALTH RELEVANCE: Healthy hearing relies upon mechanical boosting of the response within the inner ear (cochlea). In ears in which cochlear mechanics are damaged due to overstimulation, chemotherapies or simply aging the boosting is reduced or eliminated, leading to hearing loss. With the advent of genetic engineering, mouse models are being developed in which specific components of the cochlea are modified. This leads to many possibilities to explore the workings of the healthy cochlea and the ways to repair a damaged cochlea. In this project, the foundation for such advances is laid by measuring the mechanical responses of the cochleae of normal mice.

描述（由申请人提供）：哺乳动物听觉处理的两个基本事实是：（1）听觉神经中存在的频率选择性是由于耳蜗中的机械预处理，以及（2）耳蜗的力学是高度非线性的。在接近该位置的最佳频率的低声压级下，相干非线性可以提高机械响应。因此，耳蜗的非线性是耳蜗的频率选择性的核心。在机械受损的耳朵中（通过过度刺激，一些化疗，以及简单的老化），非线性降低或消除，导致听力严重丧失。关于产生耳蜗非线性的微机械作用和相互作用，被称为“耳蜗放大器”，还有很多东西需要了解。“通过基因工程改变细胞和非细胞耳蜗成分的小鼠模型已经开发出来，并已被用于促进我们对耳蜗力学的理解。然而，在历史上，小鼠不用于耳蜗力学和强大的规范性数据是缺乏的。我们建议测量声刺激后小鼠正常脑内压力和运动。这些是对正常刺激的基本反应。我们还将测量电流刺激时的压力和运动，电流刺激与声学刺激相似，在某些方面与声学刺激互补，并且已经用于改良小鼠研究，结果令人感兴趣。在建立了强有力的规范性结果后，我们计划在未来的项目中继续研究具有转基因耳蜗组件的小鼠。 公共卫生相关性：健康的听力依赖于内耳（耳蜗）内反应的机械增强。在由于过度刺激、化疗或简单老化而导致耳蜗机械受损的耳朵中，增强被减少或消除，导致听力损失。随着基因工程的出现，正在开发小鼠模型，其中耳蜗的特定组件被修改。这为探索健康耳蜗的工作方式和修复受损耳蜗的方法提供了许多可能性。在这个项目中，通过测量正常小鼠耳蜗的机械反应，为这种进步奠定了基础。