Intracochlear measures of active cochlear mechanics

描述（由申请人提供）：哺乳动物听觉加工的两个基本事实是：(1)听觉神经中存在的频率选择性是由于耳蜗的机械预处理；(2)耳蜗的力学是高度非线性的。人工耳蜗的非线性工作原理是在接近最佳频率的低声压水平下提高机械响应。因此，耳蜗非线性是耳蜗频率选择性的核心。在力学受损的耳朵中（由于过度刺激、一些化疗或单纯的老化），非线性被减少或消除，导致听力敏锐度的严重丧失。关于产生耳蜗非线性的微机械作用和相互作用（称为“耳蜗放大器”），还有很多有待研究。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，并已用于促进我们对耳蜗力学的理解。然而，从历史上看，小鼠没有被用于耳蜗力学，缺乏可靠的规范数据。我们建议在声音刺激下测量小鼠的正常耳蜗内压力和运动。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，这与声音刺激相似，在某些方面是互补的，并且已经在改良小鼠研究中使用，并取得了有趣的结果。在建立健全的规范结果后，我们计划在未来的项目中继续研究具有转基因耳蜗部件的小鼠。

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.