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1000万美国人遭受噪声引起的听力损失（NIHL）。在某些“正常”工作和生活环境中，短期和长期的噪声暴露是一个主要危害。噪声暴露，具体取决于强度和持续时间，可能导致暂时或永久的听觉阈值移位（TTS，PTS）。最近的研究表明，突触功效在腹侧腹侧耳蜗核（AVCN）的末端骨突触中恶化，而与年龄相关的听力损失的小鼠菌株中。此外，在突触后灌注神经元中，夹带到高频刺激的功能降低。这些变化可能是由于传入听觉神经纤维的活性减少所致。另一方面，噪声侮辱会在听觉神经中产生反复出现的短期多动症。过度的激发可能会对末端突触及其突触后靶标有不利影响。由于AVCN为更高的听觉中心提供了重要的线索，以了解声音定位和语音识别，因此必须了解第一次继电器突触中噪声引起的听力损失的功​​能后果。因此，我们提出了2个具体目标。在第一个目标中，我们将明确检验以下假设：噪声暴露后立即损害了末端末端的突触功效。但是，功效以中等侮辱而恢复，仅导致TT，而疗效在NIHL中使用PTS永久降低。我们将利用近交CBA小鼠中噪声暴露结果的个体变异性较低。使用改良的整个耳蜗核切片制剂，我们将在噪声过度暴露后用电生理记录进行突触传播的几个方面。在第二个目标中，我们将检验以下假设：噪声诱导的听力损失会影响突触后灌注神经元中低阈值K+电导（LLT）。这种效果反过来降低了这些神经元中的时间编码能力。我们将在诱导NIHL后从浓密的细胞中表征LLT，并通过在切片中使用逼真的泊松分布式尖峰列来激活听觉神经纤维来测试浓密的细胞的精细时间编码。该项目的数据将补充并增强有关噪声引起的听力损失的外围影响的现有信息。最终，我们要解决中央听觉途径的完整性是否可以通过NIHL后的药物或设备干预来保存，因为CNS功能完整性是成功后听力损失干预措施的重要组成部分。