Behavioral and physiological consequences of auditory nerve loss

听神经丧失的行为和生理后果

• 批准号: 10434851
• 负责人: Kenneth Stuart Henry
• 金额: $ 32.73万
• 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/10434851
• 关键词: Acoustic Nerve; Affect; Age; Animals; Auditory Perception; Auditory Threshold; Auditory system; Behavioral; Biological Models; Birds; 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; Neuraxis; Neurons; Noise; Operant Conditioning; Pathology; Pathway interactions; Pattern; Perception; Performance; Periodicity; 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; neurophysiology; relating to nervous system; response; 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.

耳蜗螺旋神经节神经元的永久性缺失是人类普遍存在的耳蜗病理 这不会影响安静时的临床听力阈值。听觉通路的感觉输入减少 可能会降低受影响个体的言语感知能力，但支持这一假设的是 不清楚这项研究的目的是查明AN损伤对听觉感知的影响 并描述感知障碍背后的生理变化。许多自然信号，包括 语音，包含幅度调制（以下称为“调制”）复杂模式， 调节中枢神经系统的神经元。调制调谐出现在中脑， 抑制，并且可以通过将竞争声音分离成离散的声音来在噪声中发挥关键的处理作用。 基于调制频率的差异来处理流。根据先前发现的 AN损伤后的抑制信号，拟议的研究将测试AN损伤的假设， 选择性地损害噪声中的复合信号感知，同时由于 神经调制调谐行为和神经生理学研究将在虎皮鹦鹉中进行， 能够模仿语言的鸟类模式物种。虎皮鹦鹉模型系统的优势包括人类- 比如复杂听力任务的行为表现和中脑处理机制， 哺乳动物，包括许多具有突出调制调谐的神经元。此外，选择性AN损伤可 使用谷氨酸类似物红藻氨酸在虎皮鹦鹉中诱导。新的行为和神经生理学 实验将研究红藻氨酸诱导的AN损伤对听觉处理的影响。目标1将 在经过行为训练的动物中使用操作性条件反射程序来识别听觉感知的各个方面 受到伤害的影响。初步数据支持我们的假设，即AN损伤对 安静时的测听阈值还可能损害依赖于调制调谐的任务的性能。目标2将 在清醒的动物中使用细胞外中脑记录来量化AN损伤对神经抑制的影响， 调制调谐以及在竞争噪声中对复杂的类语音信号进行编码。我们假设， 损伤将由于抑制减弱而降低调制调谐的强度， 噪音中合成元音和辅音的编码。Aim 3将使用单光纤AN记录来测试 假设虎皮鹦鹉的AN反应特性与哺乳动物和其他鸟类相似 物种，具有较高的阈值纤维失去以下红藻氨酸曝光。将使用新的生理结果 来完善皮层下听觉处理的计算模型。这些目标的实现将为 关键的洞察到AN损伤对简单和复杂声音的听觉感知的影响， 与感知障碍相关的神经处理变化。了解这些影响是一个 这是制定知情的公共卫生战略以治疗这种常见耳蜗病变的重要一步。