Effect of Noise Induced Hearing Loss on AVCN Principal Neurons

噪声性听力损失对 AVCN 主神经元的影响

• 批准号: 7197353
• 负责人: YONG WANG
• 金额: $ 1.78万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7197353
• 关键词: Ablation; Acoustic Nerve; Acoustics; Acute; Address; Affect; American; Animal Model; Anterior; Auditory; Auditory system; Brain Stem; Cell Nucleus; Cells; Chromosome Pairing; Chronic; Class; Cochlear nucleus; Code; Complement; Computer information processing; Condition; Control Animal; Cues; Data; Deterioration; Devices; Environment; Exhibits; Frequencies; Genetic Predisposition to Disease; Hand; Hearing; Hearing Impaired Persons; Hyperactive behavior; Immunohistochemistry; Inbred CBA Mice; Inbred DBA Mice; Individual; Intervention; Knowledge; Labyrinth; Learning; Life; Long-Term Effects; Mammals; Measures; Mouse Strains; Mus; Nerve Fibers; Neurons; Noise; Noise-Induced Hearing Loss; Outcome; Peripheral; Pharmaceutical Preparations; Physiological; Play; Potassium Channel; Preparation; Presbycusis; Process; Proteomics; Role; Slice; Sound Localization; Synapses; Synaptic Transmission; Synaptic Vesicles; Techniques; Testing; Tissues; Training; Week; Work; auditory pathway; auditory threshold shift; deafness; early onset; hazard; hearing impairment; postsynaptic; presynaptic; receptor function; research study; response; speech recognition; stem; transmission process; voltage

DESCRIPTION (provided by applicant): More than 10 million Americans suffer from noise induced hearing loss (NIHL). Short and long term noise exposure is a major hazard in certain "normal" working and living environments. Noise exposure, depending on intensity and duration, can result in temporary or permanent auditory threshold shift (TTS, PTS). Recent studies have shown that synaptic efficacy deteriorates at the endbulb synapse in the anterior ventral cochlear nucleus (AVCN) in a strain of mice with age-related hearing loss. Furthermore, there is a functional reduction of entrainment to high frequency stimulation in postsynaptic bushy neurons. These changes are likely due to diminished activity in the afferent auditory nerve fibers. Noise insults, on the other hand, generate recurring short term hyperactivity in the auditory nerve. The excessive excitation could have detrimental effect on the endbulb synapse and its postsynaptic target. Because the AVCN provides vital cues to higher auditory centers for sound localization and speech recognition, it is essential to understand the functional consequences of noise induced hearing loss at this first relay synapse. Thus, we propose 2 specific aims. In the first aim, we will explicitly test the hypothesis that synaptic efficacy at the endbulb terminal is impaired immediately following noise exposure; however, the efficacy recovers with moderate insults resulting in only TTS, whereas the efficacy becomes permanently reduced in NIHL with PTS. We will take advantage of the low individual variability in noise exposure outcome in inbred CBA mice. Using a modified whole cochlear nucleus slice preparation, we will probe several aspects of synaptic transmission with electrophysiological recordings after noise overexposure. In the second aim, we will test the hypothesis that noise induced hearing loss affects the low threshold K+ conductance (lLT) in the postsynaptic bushy neurons; this effect in turn reduces the temporal coding capability in these neurons. We will characterize the lLT from bushy cells after inducing NIHL, and test the fine temporal coding of the bushy cell by activating the auditory nerve fiber with a realistic Poisson distributed spike train in the slice. Data from this project will complement and enhance the existing wealth of information regarding the peripheral effect of noise induced hearing loss. Ultimately we would like to address whether the integrity of the central auditory pathway can be preserved with drug or device intervention after NIHL, because CNS functional integrity is an essential component of successful post hearing loss intervention.

描述（由申请人提供）：超过1000万美国人患有噪音性听力损失（NIHL）。在某些“正常”的工作和生活环境中，短期和长期的噪音暴露是一种主要危害。噪声暴露，取决于强度和持续时间，可导致暂时或永久的听觉阈值移位（TTS， PTS）。最近的研究表明，在一种与年龄相关的听力损失小鼠中，前腹侧耳蜗核（AVCN）终末球突触的突触功能恶化。此外，在突触后丛状神经元中，高频刺激诱导的功能减少。这些变化可能是由于传入听觉神经纤维活动减弱所致。另一方面，噪音的侮辱会在听觉神经中产生反复出现的短期过度活跃。过度兴奋会对终球突触及其突触后靶点产生不利影响。由于AVCN为声音定位和语音识别的高级听觉中心提供了重要的线索，因此了解噪音引起的听力损失在第一个中继突触的功能后果是必要的。因此，我们提出了两个具体目标。在第一个目标中，我们将明确地检验假说，即终球末端的突触效能在噪声暴露后立即受损；然而，在中度损伤导致TTS时，疗效恢复，而在NIHL合并PTS时，疗效永久性降低。我们将利用低个体可变性噪音暴露结果在近亲繁殖的CBA小鼠。使用改进的全耳蜗核切片制备，我们将探索噪声过度暴露后电生理记录的突触传递的几个方面。在第二个目标中，我们将验证噪声引起的听力损失影响突触后丛状神经元的低阈值K+电导（lLT）的假设；这种效应反过来又降低了这些神经元的时间编码能力。我们将在诱导NIHL后对丛状细胞的lLT进行表征，并通过在切片上使用真实的泊松分布尖峰序列激活听神经纤维来测试丛状细胞的精细时间编码。这个项目的数据将补充和加强现有关于噪音引起的听力损失的周边影响的丰富信息。最终，我们希望解决NIHL后是否可以通过药物或设备干预来保持中枢听觉通路的完整性，因为中枢神经系统功能完整性是听力损失后干预成功的重要组成部分。