Understanding the dynamics of cochlear amplification

了解耳蜗放大的动力学

• 批准号: 10168888
• 负责人: Karolina Charaziak
• 金额: $ 5.39万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10168888
• 关键词: Acoustic Trauma; Address; Affect; Algorithms; Amplifiers; Animal Model; Animals; Apical; Auditory system; Back; Basilar Membrane; Biological Assay; California; Characteristics; Cochlea; Communities; Complex; Data; Dependence; Development; Diagnosis; Diagnostic tests; Environment; Exhibits; Faculty; Frequencies; Goals; Hearing; Hearing Aids; Hearing Tests; Human; Impairment; Individual; Institution; Intervention; Knowledge; Location; Measurable; Measurement; Measures; Mechanics; Mentors; Modeling; Motion; Motor; Mus; Neurosciences; Nonlinear Dynamics; Optical Coherence Tomography; Organ of Corti; Outer Hair Cells; Peripheral; Phase; Positioning Attribute; Process; Recording of previous events; Research; Role; Sensorineural Hearing Loss; Shapes; Signal Transduction; Speech; Speech Intelligibility; Stimulus; Structure; Study models; Surface; System; Testing; Theoretical model; Time; Training; Transgenic Mice; Universities; Work; auditory processing; career development; improved; in vivo; insight; mathematical model; mechanical properties; mouse model; mutant; noninvasive diagnosis; novel diagnostics; otoacoustic emission; preservation; public health relevance; response; skills; sound; tool; transmission process; treatment strategy

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.

项目摘要 耳蜗作为一个非线性放大器，提高机械灵敏度和频率调谐在低，但 而不是高刺激水平。虽然耳蜗对音调的反应已经得到了很好的研究，但相对而言知之甚少 关于动态（即，时变）方面，如其延迟和相关的 时间常数放大器的这些特性对于理解放大器如何 诸如语音的动态刺激由外围听觉系统编码。拟议研究 结合了耳内振动测量、耳声发射（OAE）和 在动物模型中研究非线性耳蜗放大动力学的理论建模。K99 指导研究将调查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处获得的体内振动测量 外毛细胞的表面-耳蜗放大器的细胞马达。OAE的平行测量 将探测它们作为扩增过程的动力学特征的非侵入性测定的能力。 数学模型将有助于理解耳蜗放大延迟的机制及其在 塑造OAE。R 00独立研究将通过进一步剖析 通过对具有良好听力的动物的研究， 明确的损伤（声损伤）或耳蜗结构异常（转基因小鼠）。 这些结果预计将产生很大的影响，因为它们将首次揭示机制 耳蜗放大的动力学基础。通过将OAE结果与 同样的动物，这项工作将建立耳声发射作为耳蜗动力学的非侵入性测定的实用性。 处理.在更广泛的背景下，这些数据将提供洞察周边处理的贡献 听觉的时间现象，随着感官听力损失而退化，因此将奠定必要的 为制定旨在恢复现实中听觉处理的干预策略奠定基础 动态环境。 拟议研究的K99阶段将帮助候选人的职业发展，向她介绍 在体内耳蜗振动测量和扩大她有限的培训数学建模。和她一起 在OAE测量的广泛背景下，这些新技能将使候选人处于有利地位， 独立工作，以实现她的长期目标，促进我们对耳蜗力学的理解， 利用其在OAE信号中的表现来改善听力的非侵入性测试。南部大学 加州是K99研究的绝佳环境，因为该机构拥有活跃的听证会 神经科学界，包括导师，公认的专家在耳蜗力学，和其他教师。