Auditory nerve central synaptopathy during noise-induced hearing loss

噪声性听力损失期间的听觉神经中枢突触病

• 批准号: 10412432
• 负责人: Ruili Xie
• 金额: $ 15.75万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10412432
• 关键词: Acoustic Nerve; Affect; Auditory; Auditory system; Brain; Cells; Clinical; Clinical Treatment; Cochlea; Cochlear nucleus; Data; Dyes; Ear; Electrophysiology (science); Failure; Feedback; Functional disorder; General Population; Goals; Hearing; Hyperacusis; Immunohistochemistry; Impairment; Intervention; Knowledge; Lead; Membrane; Morphology; Mus; Neurons; Noise; Noise-Induced Hearing Loss; Outcome; Output; Pathologic; Peripheral; Physiological; Physiology; Population; Presbycusis; Property; Research; Structure; Synapses; Synaptic Transmission; Testing; Time; Transgenic Mice; auditory nuclei; auditory processing; cochlear synaptopathy; hearing impairment; hidden hearing loss; inhibitory neuron; neural network; normal hearing; patch clamp; relating to nervous system; response; signal processing; sound; speech recognition; spiral ganglion; transmission process; Acoustic Nerve; Affect; Auditory; Auditory system; Brain; Cells; Clinical; Clinical Treatment; Cochlea; Cochlear nucleus; Data; Dyes; Ear; Electrophysiology (science); Failure; Feedback; Functional disorder; General Population; Goals; Hearing; Hyperacusis; Immunohistochemistry; Impairment; Intervention; Knowledge; Lead; Membrane; Morphology; Mus; Neurons; Noise; Noise-Induced Hearing Loss; Outcome; Output; Pathologic; Peripheral; Physiological; Physiology; Population; Presbycusis; Property; Research; Structure; Synapses; Synaptic Transmission; Testing; Time; Transgenic Mice; auditory nuclei; auditory processing; cochlear synaptopathy; hearing impairment; hidden hearing loss; inhibitory neuron; neural network; normal hearing; patch clamp; relating to nervous system; response; signal processing; sound; speech recognition; spiral ganglion; transmission process

PROJECT SUMMARY/ABSTRACT Sound information is transmitted from the peripheral cochlea to the central auditory system via two key synapses, including the cochlear synapse and auditory nerve (AN) synapse, which are the peripheral and central endings of the spiral ganglion neurons (SGNs), respectively. Selective cochlear synaptopathy among different subtypes of SGNs has been recognized as a main mechanism of hearing loss, one of the most common forms of which is noise-induced hearing loss (NIHL). Cochlear synapses from SGNs of the low spontaneous rate/high threshold subtype are especially vulnerable and can be preferentially damaged by even moderate noise insult, which are likely the primary cause of the perceptual deficit, especially during hidden hearing loss. At the SGN central endings, however, the mechanisms of NIHL remain largely unclear. Little is known about how AN synapses from different subtypes of SGNs change in morphology and physiology during NIHL, and how such central synaptopathy contributes to the central processing deficits in target neurons in the cochlear nucleus (CN). The long-term goal of this project is to elucidate the mechanisms of NIHL at different subtypes of AN synapses and their target CN neurons. Our overall hypothesis is that AN synapses from different subtypes of SGNs have unique synaptic properties, target distinct populations of CN neurons that are dedicated to processing different aspects of sound information, and subject to different levels of synaptopathy during NIHL that lead to distinctive central auditory processing deficits among associated CN neurons. Combining electrophysiology with immunohistochemistry using transgenic mice, this project investigates selective synaptopathy at different subtypes of AN synapses during NIHL, as well as the associated central processing deficits in their target CN neurons. In Aim1, we will identify AN central synaptopathy both morphologically and physiologically at the giant endbulb of Held synapses from three subtypes of type I SGNs after two different levels of noise damage. In Aim 2, we will elucidate the mechanisms of central processing deficits in CN bushy neurons following selective AN synaptopathy during NIHL. In Aim 3, we will elucidate the mechanisms of NIHL in CN inhibitory neural network by characterizing synaptopathy of AN bouton synapses onto D-stellate neurons and clarifying the changes of their output inhibition onto CN bushy neurons during NIHL, especially hidden hearing loss. The outcome of the project will fill our knowledge gap on AN central synaptopathy as well as the mechanisms of central processing deficits in target CN neurons during NIHL.

项目摘要/摘要 声音信息通过两个键从外围耳蜗传输到中央听觉系统 突触，包括耳蜗突触和听觉神经（AN）突触，这是外围和中央 螺旋神经神经元（SGNS）的结尾。选择性的人工耳蜗突触病 SGN的亚型已被认为是听力损失的主要机制，这是最常见的形式之一 其中是噪声引起的听力损失（NIHL）。低自发速率/高的SGN的耳蜗突触 阈值亚型特别容易受到伤害，甚至可以通过中等噪音侮辱，优先损坏 这可能是感知赤字的主要原因，尤其是在隐藏听力损失期间。在SGN 然而，中心结局，NIHL的机制在很大程度上尚不清楚。关于如何 来自不同亚型SGN的突触变化了NIHL期间形态和生理学的变化，以及如何这样 中央突触病有助于人工耳蜗核（CN）中靶神经元的中央加工缺陷。 该项目的长期目标是阐明在突触的不同亚型下NIHL的机制 及其目标CN神经元。我们的总体假设是，来自不同亚型SGN的突触具有 独特的突触特性，目标的CN神经元的不同种群，这些神经元专用于处理不同 声音信息的各个方面，并受到NIHL期间不同级别的突触病的影响，导致独特 相关CN神经元之间的中央听觉处理缺陷。将电生理学与 使用转基因小鼠进行免疫组织化学，该项目研究了不同的选择性突触病。 NIHL期间突触的亚型以及其目标CN中相关的中央处理缺陷 神经元。在AIM1中，我们将在巨型上从形态和生理上识别中央突触病 两种不同水平的噪声损害后，来自三个亚型SGN的三个亚型的持有突触的末端。目标 2，我们将阐明选择性后CN浓密神经元中中央处理缺陷的机制 NIHL期间的突触病。在AIM 3中，我们将阐明CN抑制性神经网络中NIHL的机制 通过表征BOUTON突触的突触病在D型螺纹神经元上，并阐明了变化 他们在NIHL期间对CN浓密神经元的输出抑制，尤其是隐藏的听力损失。结果 项目将填补我们对中央突触病的知识差距以及中央处理的机制 NIHL期间目标CN神经元的缺陷。