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

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.

项目总结/摘要 声音信息通过两个键从外周耳蜗传递到中枢听觉系统， 突触，包括耳蜗突触和听觉神经（AN）突触，它们是外周和中枢突触。 的螺旋神经节神经元（SGN）的末端，分别。选择性耳蜗突触病 SGN亚型已被认为是听力损失的主要机制，听力损失是最常见的形式之一， 其中一种是噪声性听力损失（NIHL）。来自低自发率/高自发率SGN的突触 阈值子类型特别脆弱，且甚至可以优先地被中等噪声损害损坏， 这可能是感知缺陷的主要原因，特别是在隐性听力损失期间。在SGN 然而，尽管NIHL的机制在很大程度上仍不清楚。很少有人知道， 来自不同SGN亚型的突触在NIHL期间在形态学和生理学上发生变化，以及这些变化是如何发生的。 中枢突触病导致耳蜗核（CN）中靶神经元的中枢处理缺陷。 本项目的长期目标是阐明不同亚型AN突触的NIHL机制 和它们的目标CN神经元。我们的总体假设是，来自不同SGN亚型的AN突触具有 独特的突触特性，靶向CN神经元的不同群体，这些神经元致力于处理不同的 声音信息的各个方面，并在NIHL期间受到不同水平的突触病变，导致不同的 相关CN神经元的中枢听觉处理缺陷。将电生理学与 免疫组织化学使用转基因小鼠，该项目研究选择性突触病在不同的 NIHL期间AN突触的亚型，以及其靶CN中相关的中枢处理缺陷 神经元在Aim 1中，我们将从形态学和生理学上识别巨人的中枢突触病 在两种不同水平的噪声损伤后，来自I型SGN的三种亚型的Held突触的端球。在Aim中 2、我们将阐明选择性AN后CN丛状神经元中枢处理缺陷的机制 NIHL期间的突触病。目的3：阐明CN抑制性神经网络中NIHL的机制 通过表征AN终扣突触对D-星状神经元的突触病变， 在NIHL过程中，它们对CN丛状神经元的输出抑制，尤其是隐性听力损失。的结果 该项目将填补我们对AN中枢突触病以及中枢处理机制的知识空白 NIHL期间靶CN神经元的缺陷。