Understanding the dynamics of cochlear amplification

项目总结 耳蜗起到了非线性放大器的作用，提高了机械灵敏度和频率调谐在低但 不是高刺激水平。虽然对声调的耳蜗反应已经有了很好的研究，但相对来说知之甚少 关于这一放大过程的动态(即，时变)方面，例如它的延迟和相关 时间常数。放大器的这些特性对于理解如何 动态刺激，如语音，由外围听觉系统编码。拟议的研究 结合了耳内测振、耳声发射(OAES)和 在动物模型中建立理论模型来研究非线性耳蜗声放大的动力学。K99 指导性研究将通过以下方式研究放大器的时间动力学和主动微观力学 在Corti器官内靠近顶部和底部的两个位置进行活体振动测量 外毛细胞的表面--耳蜗放大器的细胞马达。耳声发射的平行测量 将探索它们作为扩增过程动态特征的非侵入性分析的能力。 数学模型将有助于理解耳蜗放大延迟的机制及其在脑电活动中的作用 塑造OAE。R00独立研究将扩展K99阶段的发现，进一步剖析 通过对患有良好听力障碍的动物的研究，探讨其耳蜗声放大的动力学特征。 耳蜗结构的明确损伤(听觉损伤)或异常(转基因小鼠)。 这些结果预计将产生很大的影响，因为它们将率先揭示这些机制 在耳蜗放大的动力学基础上。通过将OAE结果与 同样的动物，这项工作将确立耳声发射作为耳蜗动力学的非侵入性分析的实用性 正在处理。在更广泛的背景下，这些数据将提供对外围处理的贡献的洞察 随着感觉性听力丧失而退化的暂时性听力现象，因此将为 开发干预策略的基础，旨在恢复现实中的听觉处理 动态环境。 拟议研究的K99阶段将通过向候选人介绍以下方面来帮助她的职业发展 通过扩大她有限的数学建模训练，她在活体耳蜗测振方面取得了很大进展。和她一起 在耳声发射测量方面有广泛的背景，这些新技能将使应聘者在 独立地朝着她的长期目标努力，即提高我们对耳蜗力学和 利用其在耳声发射信号中的表现来改进听力的非侵入性测试。南加州大学 加州是K99研究的优秀环境，因为该机构拥有积极的听证会 神经科学界，包括导师，公认的耳蜗力学专家和其他教职员工。

PROJECT SUMMARY The cochlea acts as a nonlinear amplifier that boosts mechanical sensitivity and frequency tuning at low but not high stimulus levels. Although cochlear responses to tones have been well studied, relatively little is known about the dynamic (i.e., time-varying) aspects of this amplification process, such as its delays and associated time constants. These characteristics of the amplifier are especially relevant for understanding details of how dynamic stimuli, such as speech, are encoded by the peripheral auditory system. The proposed research combines the complementary approaches of intracochlear vibrometry, otoacoustic emissions (OAEs), and theoretical modeling to study the dynamics of nonlinear cochlear amplification in animal models. The K99 mentored research will investigate the temporal dynamics and active micromechanics of the amplifier through in vivo vibratory measurements obtained at two locations within the organ of Corti, near the top and bottom surfaces of the outer hair cells—the cellular motors of the cochlear amplifier. Parallel measurements of OAEs will probe their ability to serve as noninvasive assays of the dynamical features of the amplification process. Mathematical models will help to understand the mechanisms of the cochlear amplification delay and its role in shaping OAEs. The R00 independent research will extend the K99-phase findings by further dissecting the mechanisms underlying the dynamical features of cochlear amplification through studies in animals with well- defined damage (acoustic trauma) or abnormality in cochlear structures (transgenic mice). These results are expected to have a high impact because they will be first to reveal the mechanisms underlying the dynamics of cochlear amplification. By relating the OAE results to the vibrometry data in the same animals, the work will establish the utility of OAEs as noninvasive assays of the dynamics of cochlear processing. In the broader context, these data will provide insights into contributions of peripheral processing to temporal phenomena of hearing that degrade with sensory hearing loss and thus will lay the necessary groundwork for developing intervention strategies aimed at restoring auditory processing in the realistic dynamic environments. The K99 phase of the proposed research will aid the candidate’s career development by introducing her to in vivo cochlear vibrometry and by expanding her limited training in mathematical modeling. Together with her extensive background in OAE measurements, these new skills will put the candidate in a strong position to work independently toward her long-term goals of advancing our understanding of cochlear mechanics and exploiting its manifestation in OAE signals to improve noninvasive tests of hearing. The University of Southern California is an outstanding environment for the K99 research because the institution has an active hearing neuroscience community, including the mentors, recognized experts in cochlear mechanics, and other faculty.