Behavioral and physiological consequences of auditory nerve loss

听神经丧失的行为和生理后果

• 批准号: 10766343
• 负责人: Kenneth Stuart Henry
• 金额: $ 3.75万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10766343
• 关键词: Acoustic Nerve; Affect; Age; Animals; Auditory Perception; Auditory Threshold; Auditory system; Behavioral; Biological Models; Birds; Central Nervous System; Clinical; Cochlea; Code; Complex; Computer Models; Data; Detection; Discrimination; Fiber; Frequencies; Glutamates; Goals; Hair Cells; Health; Hearing; Hearing Tests; Human; Impairment; Individual; Kainic Acid; Knowledge; Learning; Mammals; Masks; Melopsittacus; Methods; Midbrain structure; Modeling; Nerve Fibers; Neural Inhibition; Neurons; Noise; Operant Conditioning; Pathology; Pathway interactions; Pattern; Perception; Performance; Periodicals; Persons; Physiological; Play; Population; Procedures; Process; Property; Public Health; Recording of previous events; Research; Research Project Grants; Role; Sensorineural Hearing Loss; Signal Detection Analysis; Signal Transduction; Speech; Speech Discrimination; Speech Perception; Stimulus; Stream; Structure; Task Performances; Technology; Testing; Training; Work; analog; auditory pathway; auditory processing; awake; base; behavioral impairment; behavioral study; cell injury; cochlear lesion; combat; experience; experimental study; extracellular; improved; innovation; insight; mouse model; nerve damage; nerve injury; neural; neurophysiology; response; segregation; sensory input; signal processing; sound; spiral ganglion; therapy development

Permanent loss of auditory-nerve (AN) spiral ganglion neurons is a prevalent cochlear pathology in humans that does not impact clinical audiometric thresholds in quiet. Reduced sensory input to the auditory pathway could potentially degrade speech-perception abilities in affected individuals, but support for this hypothesis is unclear. The goal of the proposed study is to pinpoint aspects of auditory perception impacted by AN damage and characterize the physiological changes underlying perceptual impairment. Many natural signals, including speech, contain complex patterns of amplitude modulation (hereafter, ‘modulation’) that are processed by modulation-tuned neurons in the central nervous system. Modulation tuning emerges in the midbrain due to inhibition, and can play a key processing role in noise by segregating competing sounds into discrete processing streams based on differences in modulation frequency. Building upon prior findings of diminished inhibitory signaling following AN injury, the proposed research will test the hypothesis that AN damage selectively impairs complex-signal perception in noise while sparing audiometric thresholds due to a deficit in neural modulation tuning. Behavioral and neurophysiological studies will be conducted in the budgerigar, an avian model species capable of mimicking speech. Strengths of the budgerigar model system include human- like behavioral performance on complex-listening tasks and midbrain processing mechanisms shared with mammals, including many neurons with prominent modulation tuning. Furthermore, selective AN damage can be induced in budgerigars using the glutamate analog kainic acid. New behavioral and neurophysiological experiments will investigate the impact of kainic-acid induced AN damage on auditory processing. Aim 1 will use operant-conditioning procedures in behaviorally trained animals to identify aspects of auditory perception impacted by AN damage. Preliminary data support our hypothesis that AN damage has no effect on audiometric thresholds in quiet yet can impair performance of tasks that rely on modulation tuning. Aim 2 will use extracellular midbrain recordings in awake animals to quantify effects of AN damage on neural inhibition, modulation tuning, and encoding of complex speech-like signals in competing noise. We hypothesize that AN damage will reduce the strength of modulation tuning due to diminished inhibition, and consequently degrade encoding of synthetic vowels and consonants in noise. Aim 3 will use single-fiber AN recordings to test the hypothesis that AN response properties in budgerigars are similar to those found in mammals and other avian species, with higher-threshold fibers lost following kainic-acid exposure. New physiological results will be used to refine a computational model of subcortical auditory processing. Completion of these aims will provide crucial insight into the impact of AN damage on auditory perception of simple and complex sounds and the changes in neural processing associated with perceptual impairment. Understanding these effects is an essential step toward developing an informed public health strategy to treat this common cochlear pathology.

听觉神经（AN）螺旋神经神经元的永久丧失是人类普遍的人工耳蜗病理学 这不会影响安静的临床听觉阈值。减少了听觉途径的感觉输入 可能会降低受影响个体的语音感知能力，但对此假设的支持是 不清楚。拟议的研究的目的是指出受损害影响的听觉感知方面 并表征感知障碍的物理变化。许多自然信号，包括 语音，包含由放大器调制的复杂模式（以下简称为“调制”） 中枢神经系统中的调节神经元。由于 抑制作用，可以通过将竞争声音隔离为离散来在噪声中发挥关键的处理作用 基于调制频率的差异处理流。基于先前发现的发现 受伤后的抑制信号传导，拟议的研究将检验损害的假设 由于防御的防御 神经调节调整。行为和神经生理研究将在Budgerigar中进行 能够模仿语音的鸟类模型物种。预算模型系统的优势包括人类 像在复杂上符合任务和中间脑处理机制上的行为表现一样 哺乳动物，包括许多具有突出调节的神经元。此外，选择性损害可以 使用谷氨酸类似的海藻酸在BuceparyGars中诱导。新的行为和神经生理学 实验将研究迦尼酸的影响会引起对听觉处理的损害。目标1意志 在受行为训练的动物中使用操作条件程序来识别听觉感知的各个方面 受损害的影响。初步数据支持我们的假设，即损害对 安静的听力学阈值可以损害依赖调制调整的任务的性能。 AIM 2意志 在清醒动物中使用细胞外中脑记录来量化损害对神经抑制的影响， 调制调整，并在竞争噪声中编码复杂的语音信号。我们假设 损坏将降低由于抑制减少而导致调制的强度，从而降低 噪声中合成元音和辅音的编码。 AIM 3将使用单纤维和录音来测试 假设预算架中的响应特性与哺乳动物和其他禽类相似 物种，高阈值纤维在迦尼酸暴露后损失。将使用新的生理结果 优化皮层听觉处理的计算模型。这些目标的完成将提供 对损害对简单和复杂声音听觉感知的影响的关键见解以及 与知觉障碍相关的神经加工的变化。了解这些效果是 制定知情的公共卫生战略以治疗这种常见的人工耳蜗病理学的重要步骤。