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Behavioral and physiological consequences of auditory nerve loss

听神经丧失的行为和生理后果

基本信息

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
项目类别：
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

项目摘要

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）螺旋神经节神经元的永久性损失是一种普遍的人类耳蜗病理