Intracochlear measures of active cochlear mechanics

描述(申请人提供)：哺乳动物听觉处理的两个基本事实是：(1)存在于听神经中的频率选择性是由于耳蜗中的机械预处理和(2)耳蜗力学是高度非线性的。耳蜗非线性性的作用是在接近位置最佳频率的低声压级下提高机械响应。因此，耳蜗线性度是耳蜗线频率选择性的核心。在机械受损的耳朵中(通过过度刺激、一些化疗和简单的衰老)，非线性被减少或消除，导致严重的听力丧失。关于产生耳蜗非线性度的微机械作用和相互作用，还有很多需要了解的地方，称为“耳蜗放大器”。通过基因工程改变细胞和非细胞耳蜗组分的小鼠模型已经被开发出来，并且已经被用来促进我们对耳蜗力学的理解。然而，从历史上看，老鼠并不是用于耳蜗力学的，缺乏强有力的标准化数据。我们建议测量小鼠在声刺激下的正常脑白质内压力和运动。这些是对正常刺激的基本反应。我们还将测量电流刺激下的压力和运动，这类似于声刺激，并在某些方面与声刺激互补，并已用于改进的小鼠研究，得到了有趣的结果。一旦建立了可靠的标准化结果，我们计划在未来的项目中继续研究带有转基因耳蜗组分的小鼠。 与公共健康相关：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、化疗或单纯老化而导致耳蜗机能受损的耳朵中，助推作用会减少或消除，导致听力损失。随着基因工程的到来，正在开发的小鼠模型中，耳蜗的特定成分被修改。这带来了许多可能性，可以探索健康耳蜗的工作原理，以及修复受损耳蜗的方法。在这个项目中，通过测量正常小鼠的耳蜗力学反应为这些进展奠定了基础。

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.