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（申请人提供）：超过1000万美国人患有噪声性听力损失（NIHL）。在某些“正常”的工作和生活环境中，短期和长期的噪声暴露是一种主要的危害。噪声暴露，取决于强度和持续时间，可以导致暂时或永久的听阈移位（TTS，PTS）。最近的研究表明，在与年龄相关的听力损失的小鼠品系中，前腹侧耳蜗核（AVCN）中的球内突触的突触效能恶化。此外，在突触后丛神经元中，对高频刺激的夹带功能减少。这些变化可能是由于传入听觉神经纤维的活动减少。另一方面，噪声损伤会在听觉神经中产生反复出现的短期过度活跃。过度兴奋可对球内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线索，因此必须了解噪声引起的听力损失在第一个中继突触处的功能后果。因此，我们提出了两个具体目标。在第一个目标中，我们将明确测试的假设，即在endbulb终端的突触功效受损后立即噪声暴露，然而，疗效恢复与中度侮辱导致只有TTS，而疗效成为永久性降低NIHL与PTS。我们将利用近交CBA小鼠噪声暴露结果的低个体变异性。我们将使用改良的全耳蜗核切片制备方法，通过电生理记录探讨噪声过度刺激后突触传递的几个方面。在第二个目标中，我们将测试的假设，噪声引起的听力损失影响低阈值K+电导（lLT）在突触后神经元，这种影响反过来又降低了这些神经元的时间编码能力。我们将表征诱导NIHL后来自丛状细胞的lLT，并通过在切片中用真实的泊松分布的尖峰序列激活听觉神经纤维来测试丛状细胞的精细时间编码。该项目的数据将补充和加强现有的关于噪声性听力损失周边效应的信息。最终，我们想解决的是，在NIHL后，通过药物或器械干预是否可以保持中枢听觉通路的完整性，因为CNS功能完整性是成功的听力损失后干预的重要组成部分。