The mechanical and ionic roles of cochlear fluids in hearing and hearing loss

耳蜗液在听力和听力损失中的机械和离子作用

• 批准号: 10644985
• 负责人: Anders Fridberger
• 金额: $ 57.97万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-04-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10644985
• 关键词: Address; Age; Animals; Apical; Auditory; Auditory Physiology; Basilar Membrane; Bass; Binding Sites; Biochemical; Biological Models; Blood flow; Buffers; Calcium; Calcium ion; Cell physiology; Cells; Charge; Chemicals; Chronic; Clinical; Cochlea; Cochlear Implants; Data; Development; Endolymph; Environment; Extracellular Fluid; Frequencies; Functional disorder; Furosemide; Future; Goals; Hair Cells; Hearing; High-Frequency Hearing Loss; Human; In Vitro; Intervention; Knowledge; Laboratories; Labyrinth; Link; Liquid substance; Location; Measurement; Measures; Mechanics; Methods; Modeling; Modiolus; Molecular; Motion; Mutant Strains Mice; Nature; Neurosciences; Optical Coherence Tomography; Organ; Organ of Corti; Output; Pathology; Perfusion; Perilymph; Physiological; Physiology; Presbycusis; Process; Property; Proteins; Pump; Regulation; Research; Rest; Role; Sensory; Site; Speech; Stimulus; Stria Vascularis; Structural Protein; Structure; System; Techniques; Time; Tissues; Travel; Viscosity; Wood material; Work; confocal imaging; correctional system; design; deviant; experimental study; hearing impairment; hearing loss treatment; helicotrema; imaging modality; in vivo; innovation; insight; interest; minimally invasive; mutant; normal hearing; novel; pharmacologic; pressure; response; sound; sound frequency; stem; tectorial membrane; theories; treatment strategy; vibration

Project Summary A goal of the cochlear physiology laboratory is to understand how the components of the organ of Corti tune the sound induced vibration of the organ of Corti. A process known as cochlear amplification (CA), now the subject of intense work around the world, has critical components not yet studied. Two questions of broad interest that this proposal address are; 1) how does the fundamental hydrodynamic viscosity contribute to the unique frequency analysis capacity of the cochlear apex where speech frequencies are processed and 2) does the tectorial membrane in have a central and biochemical role in regulating the calcium ion concentration that is so critical to hair cell function. There are three Aims. New and innovative experimental approaches are needed to address these questions. For the measurement of output variables, we continue to use the optical coherence tomography (OCT) method, that we pioneered, to record inner ear tissue vibration. We use state of the art confocal imaging methods applied to whole organ explant systems and measure calcium ion concentrations in quiescent and stimulated inner ears. In Aim 1, about question 1, we also propose to determine if perilymph macroscopic viscosity is a crucial parameter of apical frequency tuning. As well as whether the tuning is dependent upon the process of cochlear amplification within the traveling wave as it propagates to the apex. To manipulate viscosity, normal perilymph is replaced with altered viscosity perilymph via a real time perfusion system. Aims 2 and 3 are about question 2 where we seek to understand how and with what consequence is calcium stored by the tectorial membrane. Involved is the use of mutant mural models of defective tectorial membrane structural proteins and quantitative fluorescent determination of calcium concentrations in endolymph and tectorial membrane. Additionally, in Aim 3, we explore how age might factor into the tectorial membrane calcium sequestration via two models that manipulate the physiology of the stria vascularis a known target of age degeneration. Model 1 is the chronic application of furosemide, an agent to suppress endocochlear potential. Model 2 is the genetically targeted chemical alteration of stria vascularis blood flow). Taken together the work will significantly advance not only fundamental knowledge of organ of Corti function but open a path to pharmacological interventions to treat tectorial membrane calcium pathology.

项目概要 耳蜗生理学实验室的目标是了解柯蒂氏器的组成部分如何调节耳蜗 声音引起的柯蒂氏器振动。称为耳蜗放大 (CA) 的过程，现在是主题 世界各地紧张工作的一部分，其关键组成部分尚未研究。两个引起广泛关注的问题 该提案的地址是； 1) 基本流体动力粘度如何有助于独特的 处理语音频率的耳蜗尖部的频率分析能力，2) 盖膜在调节钙离子浓度方面具有重要的生化作用，因此 对毛细胞功能至关重要。有三个目标。 需要新的和创新的实验方法来解决这些问题。用于测量 输出变量，我们继续使用我们首创的光学相干断层扫描（OCT）方法， 记录内耳组织的振动。我们使用最先进的共焦成像方法应用于整个器官 外植体系统并测量静止和受刺激内耳中的钙离子浓度。 在目标 1 中，关于问题 1，我们还建议确定外淋巴宏观粘度是否是一个关键因素。 顶端频率调谐参数。以及调音是否依赖于耳蜗的过程 当行波传播到顶点时，行波内的放大。控制正常外淋巴液的粘度 通过实时灌注系统用改变粘度的外淋巴液替代。目标 2 和 3 与问题 2 有关 我们试图了解盖膜储存钙的方式和后果。 涉及的是使用有缺陷的盖膜结构蛋白的突变壁模型和定量 荧光测定内淋巴和盖膜中的钙浓度。另外，在目标 3，我们通过两个模型探讨了年龄如何影响盖膜钙隔离 操纵血管纹的生理机能是年龄退化的已知目标。模型1是慢性 应用呋塞米，一种抑制耳蜗电位的药物。模型2是基因靶向 血管纹血流的化学改变）。总而言之，这项工作不仅将显着推进 柯蒂功能器官的基础知识，但开辟了一条药物干预治疗的道路 盖膜钙病理学。

项目成果

The reticular lamina and basilar membrane vibrations in the transverse direction in the basal turn of the living gerbil cochlea.

• DOI: 10.1038/s41598-022-24394-0
• 发表时间: 2022-11-17
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: He, Wenxuan;Burwood, George;Porsov, Edward, V;Fridberger, Anders;Nuttall, Alfred L.;Ren, Tianying
• 通讯作者: Ren, Tianying

Comment on "Enhancement of the transient-evoked otoacoustic emission produced by the addition of a pure tone in the guinea pig" [J. Acoust. Soc. Am. 104, 344-349 (1998)].

对“通过添加纯音对豚鼠产生的瞬态诱发耳声发射的增强”的评论 [J.

• DOI: 10.1121/1.426280
• 发表时间: 1999
• 期刊: The Journal of the Acoustical Society of America
• 作者: Ren,T;Nuttall,AL
• 通讯作者: Nuttall,AL

Inverse-solution method for a class of non-classical cochlear models.

一类非经典耳蜗模型的逆解方法。

• DOI: 10.1121/1.3083240
• 发表时间: 2009
• 期刊: The Journal of the Acoustical Society of America
• 作者: deBoer,Egbert;Nuttall,AlfredL
• 通讯作者: Nuttall,AlfredL

An outer hair cell-powered global hydromechanical mechanism for cochlear amplification.

• DOI: 10.1016/j.heares.2021.108407
• 发表时间: 2022-09-15
• 期刊: HEARING RESEARCH
• 影响因子: 2.8
• 作者: He, Wenxuan;Burwood, George;Fridberger, Anders;Nuttall, Alfred L.;Ren, Tianying
• 通讯作者: Ren, Tianying

Electrically evoked otoacoustic emissions from apical and basal perilymphatic electrode positions in the guinea pig cochlea.

豚鼠耳蜗顶端和基底外淋巴电极位置的电诱发耳声发射。

• DOI: 10.1016/s0378-5955(00)00238-0
• 发表时间: 2001
• 期刊: Hearing research
• 影响因子: 2.8
• 作者: Nuttall,AL;Zheng,J;Ren,T;deBoer,E
• 通讯作者: deBoer,E