Behavioral and physiological consequences of auditory nerve loss

听觉神经 (AN) 螺旋神经节神经元的永久性丧失是人类常见的耳蜗病理 这不会影响安静状态下的临床听力阈值。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，但对这一假设的支持是 不清楚。拟议研究的目标是查明受 AN 损伤影响的听觉感知的各个方面 并描述知觉障碍背后的生理变化。许多自然信号，包括 语音，包含复杂的幅度调制模式（以下简称“调制”），这些模式由 中枢神经系统中调节调节的神经元。由于以下原因，中脑中出现了调制调谐 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 根据调制频率的差异处理流。建立在先前发现的减少的基础上 AN 损伤后的抑制信号传导，拟议的研究将检验 AN 损伤的假设 选择性地损害噪声中的复杂信号感知，同时由于听觉阈值的缺陷而保留听力阈值 神经调制调谐。行为和神经生理学研究将在虎皮鹦鹉身上进行，虎皮鹦鹉是一种 能够模仿语言的鸟类模型物种。虎皮鹦鹉模型系统的优点包括人类 例如复杂听力任务的行为表现和与共享的中脑处理机制 哺乳动物，包括许多具有显着调制调节的神经元。此外，选择性AN损伤可以 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 AN 损坏的影响。初步数据支持我们的假设，即 AN 损伤对 安静情况下的听力阈值可能会损害依赖调制调谐的任务的性能。目标2将 使用清醒动物的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 AN 损坏会由于抑制减弱而降低调制调谐的强度，从而降低性能 噪声中合成元音和辅音的编码。 Aim 3 将使用单纤 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的反应特性相似 暴露于红藻氨酸后，纤维损失阈值较高。将使用新的生理结果 完善皮层下听觉处理的计算模型。完成这些目标将提供 深入了解 AN 损伤对简单和复杂声音的听觉感知的影响以及 与知觉障碍相关的神经处理变化。了解这些影响是一个 制定明智的公共卫生策略来治疗这种常见的耳蜗病理学是至关重要的一步。

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.