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: 7100564
• 负责人: YONG WANG
• 金额: $ 7.3万
• 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 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7100564
• 关键词: AMPA receptors; action potentials; auditory nuclei; auditory pathways; auditory stimulus; auditory threshold shift; environmental exposure; evoked potentials; glutamates; immunocytochemistry; laboratory mouse; labyrinth; nerve injury; neural information processing; neural transmission; noise biological effect; noise induced deafness; potassium channel; protein structure function; proteomics; sensory mechanism; tissue /cell culture; voltage /patch clamp

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 万美国人患有噪声性听力损失 (NIHL)。短期和长期的噪声暴露是某些“正常”工作和生活环境中的主要危害。噪声暴露（取决于强度和持续时间）可能会导致暂时或永久的听觉阈值偏移（TTS、PTS）。最近的研究表明，在患有与年龄相关的听力损失的小鼠品系中，前腹侧耳蜗核（AVCN）的端球突触的突触功效恶化。此外，突触后浓密神经元对高频刺激的夹带也有功能性减少。这些变化可能是由于传入听觉神经纤维的活动减少所致。另一方面，噪音侵害会导致听觉神经反复出现短期过度活跃。过度兴奋可能会对末球突触及其突触后目标产生有害影响。由于 AVCN 为高级听觉中心提供声音定位和语音识别的重要线索，因此了解噪声引起的听力损失在第一个中继突触的功能后果至关重要。因此，我们提出了两个具体目标。在第一个目标中，我们将明确测试这样的假设：噪声暴露后，端球末端的突触功效立即受损；然而，中度损伤仅导致 TTS 时疗效会恢复，而伴有 PTS 的 NIHL 疗效会永久降低。我们将利用近交 CBA 小鼠噪声暴露结果的低个体变异性。使用改良的整个耳蜗核切片制备，我们将在噪声过度暴露后通过电生理记录探讨突触传递的几个方面。在第二个目标中，我们将检验噪声引起的听力损失影响突触后浓密神经元中低阈值 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 后表征来自浓密细胞的 lLT，并通过在切片中使用真实的泊松分布尖峰序列激活听觉神经纤维来测试浓密细胞的精细时间编码。该项目的数据将补充和增强有关噪声引起的听力损失的外围影响的现有丰富信息。最终，我们想解决 NIHL 后是否可以通过药物或设备干预来保留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成功干预的重要组成部分。