Role of Organ of Corti Outer Hair Cell/Vibration Hot Spots in Distortion Product Otoacoustic Emission Generation

项目总结/摘要 在我们实验室的早期研究中，使用干扰音（IT）和对照组之间的矢量差异分析， 和各种实验条件下建立的大畸变产物耳声发射（DPOAEs）， 由强增强和/或抑制证明的成分，可以来自位于高达 f2主音的几个八度音阶。在沙鼠中进行的拟议实验的重点是识别一种 解释这种基础DPOAE存在的耳蜗微观力学的物理机制 件.具体而言，下文所述的研究旨在表明， 由最近描述的定位于外毛细胞（OHC）的非线性振动热点（VHS）产生 地区与BM不同，这些OHC/VHS在测量BF以下的许多倍频程上是非线性的，并且 能够产生比其对应的BM振动大得多的物理运动。方法 将利用非侵入性光学相干断层扫描（OCT），其能够测量各种物体的振动。 沿着同时记录Corti器的子成分， 产品（iDP）和耳道DPOAE。以这种方式，OHC/VHS将广泛地与非扩增性 分布式非线性假设是基本产生的DPOAE分量的来源，因此， 为它们的产生提供了直接的物理机制。简言之，目标1利用OCT表征iDP 从BM和OHC/VHS区域同时作为主色调水平和f2/f1比率的函数， 主频调在顶部步进超过OCT测量位置的最佳频率（BF）。Fourier 将执行来自BM和OHC/VHS的振动的变换，以从这些振动中提取iDP。 子组件。接下来，IT和短暂的噪声过曝光将用于线性化非放大 OHC/VHS的非线性，同时测量耳道DPOAE。矢量减法将是 用于分离假设负责产生基础DPOAE成分的成分。 在目标2中，呋塞米给药将用于暂时消除OHC/VHS和BM iDP， 从而干扰广泛分布的OHC/VHS非线性和BM放大峰值 非线性，已被证明表现出不同的恢复时间课程。通过这种方式，捐款 从BM峰值和宽带非线性可以分离。同样，基础iDP和DPOAE组分 将通过在上述干预之前和之后对这些措施进行向量减法来提取。的 这些实验的预期结果将阐明OHC/VHS在什么情况下产生iDP， 它们对耳道中通常记录的DPOAE的贡献程度。如果拟议的 实验是成功的，通过提供产生基础DPOAE的直接物理机制， 几十年的DPOAE产生的理论模型将需要重大的修改和临床DP图 可以通过用IT去除混杂的基础DPOAE成分来改善。 1

PROJECT SUMMARY/ABSTRACT Earlier research in our laboratory using interference tones (ITs) and vector-difference analyses between control and various experimental conditions established that large distortion product otoacoustic emissions (DPOAEs) components evidenced by strong enhancement and/or suppression, can arise from regions located up to several octaves basal to the f2 primary-tone. The proposed experiments in gerbils are focused on identifying a physical mechanism in cochlear micromechanics that explains the existence of such basal DPOAE components. Specifically, the studies described below are aimed at showing that basal components are produced by recently described nonlinear vibration hotspots (VHSs) that localize to the outer hair cell (OHC) region. These OHC/VHSs, unlike the BM, are nonlinear over many octaves below the measurement BF, and are capable of generating physical motions significantly larger than their counterpart BM vibrations. Methods will utilize noninvasive optical coherence tomography (OCT) that is capable of measuring vibrations of various subcomponents of the organ of Corti, along with the simultaneous recordings of intracochlear distortion products (iDPs) and ear-canal DPOAEs. In this manner, OHC/VHSs will be linked to the nonamplifying widely distributed nonlinearity hypothesized to be the source of basally generated DPOAE components, thus, providing a direct physical mechanism for their generation. Briefly, Aim 1 utilizes OCT to characterize iDPs from the BM and OHC/VHS regions simultaneously as a function of primary-tone levels and f2/f1 ratios as the primary-tones are stepped apically past the best frequency (BF) of the OCT-measurement location. Fourier transforms of the vibrations from the BM and the OHC/VHSs will be performed to extract iDPs from these subcomponents. Next, ITs and brief noise overexposures will be used to linearize the nonamplifying nonlinearity of the OHC/VHSs while simultaneously measuring ear-canal DPOAEs. Vector subtraction will be used to isolate components that are hypothesized to be responsible for generating basal DPOAE components. In Aim 2, furosemide administration will be employed to temporarily eliminate OHC/VHSs and BM iDPs, thereby interfering with both the broadly distributed OHC/VHS nonlinearity and the BM amplifying peak nonlinearity, which have been shown to exhibit different recovery-time courses. In this manner, contributions from the BM peak and broadband nonlinearities can be separated. Again, basal iDP and DPOAE components will be extracted by vector subtraction of these measures before and after the above interventions. The expected outcomes of these experiments will clarify under what circumstances OHC/VHSs produce iDPs and to what extent they contribute to the DPOAEs commonly recorded in the ear canal. If the proposed experiments are successful, by providing a direct physical mechanism for the generation of basal DPOAEs, decades of theoretical models of DPOAE generation will require significant modification and clinical DP-grams can be improved by removing the confounding basal DPOAE components with an IT.     1