Understanding the dynamics of cochlear amplification

了解耳蜗放大的动力学

• 批准号: 10531629
• 负责人: Karolina Charaziak
• 金额: $ 24.75万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10531629
• 关键词: Acoustic Trauma; Address; Affect; Algorithms; Amplifiers; Animal Model; Animals; Apical; Auditory system; Back; Basilar Membrane; Biological Assay; California; Characteristics; Cochlea; Communities; Compensation; Complex; Data; Data Analyses; 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; Non-Invasive Detection; Nonlinear Dynamics; Optical Coherence Tomography; Organ of Corti; Outer Hair Cell of the Organ of the 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.

项目概要 耳蜗充当非线性放大器，可提高机械灵敏度和低频调谐频率 尽管耳蜗对音调的反应已得到充分研究，但人们所知甚少。 关于此放大过程的动态（即随时间变化）方面，例如其延迟和相关的 放大器的这些特性对于理解放大器的细节尤其重要。 动态刺激，例如语音，是由周围听觉系统编码的。 结合了耳蜗内振动测量、耳声发射 (OAE) 和 研究动物模型中非线性耳蜗放大动力学的理论模型。 指导研究将通过以下方式研究放大器的时间动力学和有源微力学 在柯蒂氏器内两个位置（靠近顶部和底部）获得的体内振动测量 外毛细胞表面——耳蜗放大器的细胞马达 OAE 的并行测量。 将探讨它们作为扩增过程动态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 R00 独立研究将通过进一步剖析 K99 阶段的发现来扩展 OAE。 通过对具有良好功能的动物进行研究，了解耳蜗放大动态特征的机制 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重大影响，因为它们将首先揭示其机制 通过将 OAE 结果与振动测量数据相关联，揭示了耳蜗放大的动力学。 同样的动物，这项工作将建立 OAE 作为耳蜗动力学无创分析的实用性 在更广泛的背景下，这些数据将提供对外围处理的贡献的见解。 听觉的时间现象会随着感觉性听力损失而降低，因此将奠定必要的基础 制定干预策略的基础，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 体内耳蜗振动测量并与她一起扩展她在数学建模方面的有限训练。 在 OAE 测量方面拥有丰富的背景，这些新技能将使候选人处于有利地位 独立致力于她的长期目标，即增进我们对耳蜗力学的理解和 南方大学利用其在 OAE 信号中的表现来改善无创听力测试。 加州是 K99 研究的绝佳环境，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员。