Experimental study of the cochlear amplifier

人工耳蜗放大器的实验研究

• 批准号: 10222639
• 负责人: TIANYING REN
• 金额: $ 51.93万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-28 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10222639
• 关键词: Acoustics; Amplifiers; Animals; Apical; Auditory; Basic Science; Basilar Membrane; Cochlea; Custom; Data; Diagnosis; Electric Stimulation; Feedback; Frequencies; Funding; Generations; Genetically Engineered Mouse; Gerbils; Hair; Hearing; Human; In Vitro; Interferometry; Knowledge; Liquid substance; Mammals; Measurement; Measures; Mechanics; Molecular; Mus; Outer Hair Cells; Patients; Phase; Process; Production; Proteins; Research; Scanning; Series; Somatic Cell; Techniques; Testing; Travel; cell motility; experimental study; hearing impairment; heterodyning; in vivo; innovation; mutant; novel; otoacoustic emission; response; sound; tectorial membrane; tool; vibration

Project Summary/Abstract The cochlea-generated sounds, otoacoustic emissions (OAEs), have been routinely measured as a non- invasive tool for diagnosing hearing loss in humans and for studying cochlear mechanisms in experimental animals. However, underlying mechanical mechanisms of OAE generation and suppression remain unclear. Recent technological breakthroughs in low-coherence interferometry allow us to measure vibrations inside the cochlear partition in living cochleae and genetically engineered mouse models make it possible to study molecular mechanisms of cochlear micromechanics. The objective of this study is to determine the cellular origin and sub-cellular mechanisms responsible for generation of distortion product (DP) OAE (DPOAE), the most commonly used OAE, by conducting a series of novel in vivo experiments using a custom-built scanning heterodyne low-coherence interferometer. Our overarching hypothesis is that, in mammals, nonlinear mechanoelectrical transduction of outer hair cells generates electrical DPs and somatic motility converts them into mechanical DPs and DPOAEs. DPOAE suppression results from suppression of the primary tone-induced traveling waves, and the DPOAE suppression tuning curve (STC) is related to but different from cochlear mechanical tuning. This central hypothesis will be tested by conducting the following experiments. Experiment One will determine the cellular origin of DPs by measuring vibrations from the reticular lamina (RL) at the apical ends of outer hair cells and from the basilar membrane (BM) at DP frequencies in healthy cochleae. Data showing that RL DPs are larger than BM DPs will be the first in vivo demonstration that DPOAEs are generated by outer hair cells. Experiment Two will determine whether or not somatic motility of outer hair cells generates DPs in vivo by measuring RL and BM responses to electrical stimulation with two-frequency currents in alpha-tectorin protein mutant (TectaC1509G/C1509G) mice. Since these mice have functional somatic motility and ineffective hair-bundle motility and mechanoelectrical transduction due to the deformed tectorial membrane, data showing the lack of electrically evoked RL and BM DPs will indicate that somatic motility does not generate DP in vivo. The third experiment will study the mechanical mechanism of DPOAE suppression and determine the relationship between the DPOAE STC and cochlear mechanical tuning. The STC of DPOAE at 2f1-f2 will be measured and compared to the STCs of the BM f2 and RL f2 and iso-response curves of the BM and RL. The proposed experiments will demonstrate the origin of DPOAEs and reveal mechanical mechanisms of DPOAE suppression. Results on the relation of the DPOAE STC to cochlear mechanical tuning can potentially benefit patients and basic science research by gaining precise information on the cochlear active process through objective and noninvasive DPOAE measurement.

项目总结/摘要 耳蜗产生的声音，耳声发射（OAEs），已被常规测量为非- 用于诊断人类听力损失和在实验中研究耳蜗机制的侵入性工具 动物然而，OAE产生和抑制的潜在机械机制仍不清楚。 最近在低相干干涉测量方面的技术突破使我们能够测量 活耳蜗和基因工程小鼠模型中的耳蜗分区使得研究 耳蜗微力学的分子机制本研究的目的是确定细胞 起源和亚细胞机制负责产生畸变产物（DP）OAE（DPOAE）， 最常用的OAE，通过使用定制的扫描进行一系列新颖的体内实验， 外差低相干干涉仪我们的首要假设是，在哺乳动物中， 外毛细胞的机械电转导产生电DPs，体细胞运动将其转化 机械DP和DPOAE。DPOAE的抑制是由于抑制了主音诱发的 DPOAE抑制调谐曲线（STC）与耳蜗有一定的相关性，但又有一定的差异 机械调谐这一中心假设将通过以下实验进行检验。实验 将通过测量来自网状层（RL）的振动来确定DP的细胞起源。 外毛细胞的顶端和基底膜（BM）在DP频率在健康耳蜗。 显示RL DP大于BM DP的数据将首次在体内证明DPOAE是 由外毛细胞产生。实验二将确定外毛细胞的体细胞运动性 通过测量RL和BM对双频电流电刺激的反应，在体内产生DP 在α-tectorin蛋白突变体（TectaC 1509 G/C1509 G）小鼠中。由于这些小鼠具有功能性躯体 运动和无效的毛束运动和机械电转导由于变形的顶盖 由于电诱发的RL和BM DP的缺乏，表明体细胞运动确实 在体内不产生DP。第三个实验将研究DPOAE抑制的力学机制 并确定DPOAE STC与耳蜗机械调谐的关系。DPOAE的STC 将测量2f 1-f2的STC，并与BM f2和RL f2的STC以及 BM和RL。建议的实验将证明DPOAE的起源，并揭示机械 DPOAE抑制机制。DPOAE STC与耳蜗机械调谐关系的研究结果 通过获得耳蜗的精确信息， 通过客观和非侵入性的DPOAE测量，

项目成果

Probing the cochlear amplifier by immobilizing molecular motors of sensory hair cells.

通过固定感觉毛细胞的分子马达来探测耳蜗放大器。

• DOI: 10.1016/j.neuron.2012.11.016
• 发表时间: 2012
• 期刊: Neuron
• 影响因子: 16.2
• 作者: Ren,Tianying;Gillespie,PeterG
• 通讯作者: Gillespie,PeterG

Electrically evoked auditory nerve responses in the cochlea with normal outer hair cells.

电诱发耳蜗中具有正常外毛细胞的听觉神经反应。

• DOI: 10.1016/s1672-2930(09)50017-7
• 发表时间: 2009
• 期刊: Journal of otology
• 影响因子: 1.9
• 作者: Ren,Tianying;Guo,Menghe;He,Wenxuan;Miller,JosefM;Nuttall,AlfredL
• 通讯作者: Nuttall,AlfredL

Cochlear compression wave: an implication of the Allen-Fahey experiment.

耳蜗压缩波：Allen-Fahey 实验的结果。

• DOI: 10.1121/1.2177586
• 发表时间: 2006
• 期刊: The Journal of the Acoustical Society of America
• 作者: Ren,Tianying;Nuttall,AlfredL
• 通讯作者: Nuttall,AlfredL

The cochlear amplifier and Ca2+ current-driven active stereocilia motion.

耳蜗放大器和 Ca2 电流驱动主动静纤毛运动。

• DOI: 10.1038/nn0205-132
• 发表时间: 2005
• 期刊: Nature neuroscience
• 影响因子: 25
• 作者: Ren,Tianying

Loud sound-induced changes in cochlear mechanics.

大声的声音引起的耳蜗力学变化。

• DOI: 10.1152/jn.00192.2002
• 发表时间: 2002
• 期刊: Journal of neurophysiology
• 影响因子: 2.5
• 作者: Fridberger,Anders;Zheng,Jiefu;Parthasarathi,Anand;Ren,Tianying;Nuttall,Alfred
• 通讯作者: Nuttall,Alfred