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 耳蜗充当非线性放大器，在低处引导机械灵敏度和频率调整 不是高刺激水平。尽管对色调的耳蜗响应已经很好地研究了，但鲜为人知 关于此扩增过程的动态（即时变）方面，例如其延迟和相关 时间常数。放大器的这些特征与理解如何了解如何 动态刺激（例如语音）由外围听觉系统编码。拟议的研究 结合了核流振动法，耳声排放（OAE）和的完整方法 理论模型研究动物模型中非线性耳蜗扩增的动力学。 K99 Menored Research将通过 在Corti器官的两个位置获得的体内振动测量，顶部和底部附近 外毛细胞的表面 - 耳蜗放大器的细胞电动机。 OAE的平行测量 将探究其作为放大过程动态特征的无创测定能力。 数学模型将有助于了解耳蜗放大延迟的机制及其在 塑造OAE。 R00独立研究将通过进一步解剖来扩展K99相的发现 通过对具有良好良好动物的研究的研究，具有人工耳蜗扩增动态特征的机制 人工耳蜗（转基因小鼠）的定义损伤（声学创伤）或异常。 预计这些结果将产生很大的影响，因为它们将首先揭示机制 人工耳蜗放大动力学的基础。通过将OAE结果与纤维化数据相关联 同样的动物，这项工作将确定欧盟的实用性作为对耳蜗动态的无创评估 加工。在更广泛的背景下，这些数据将提供有关外围处理贡献的见解 暂时的听力现象会因感觉听力损失而降级，因此会造成必要的 制定旨在恢复现实中听觉处理的干预策略的基础工作 动态环境。 拟议研究的K99阶段将通过介绍她的职业发展，以帮助她 体内耳蜗振动法，并通过扩展其在数学建模方面的有限训练。和她一起 在OAE测量中广泛的背景，这些新技能将使候选人处于强大的位置 独立努力实现她对我们对人工耳蜗的理解的长期目标和 利用其在OAE信号中的表现，以改善听力的非侵入性测试。南方大学 加利福尼亚是K99研究的杰出环境，因为该机构有积极的听证会 神经科学社区，包括导师，公认的人工艺力学专家和其他教师。