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

基本信息

批准号：
7486435
负责人：
YONG WANG
金额：
$ 5.4万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
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/7486435
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

项目摘要

More than 10 million Americans suffer from noise induce 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 (lLr) in the postsynaptic bushy neurons; this effect in turn reduces the temporal coding capability in these neurons. We will characterize the rfrom 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.

超过 1000 万美国人患有噪音性听力损失 (NIHL)。短期和长期噪声在某些“正常”工作和生活环境中，接触是主要危险。噪声暴露，取决于强度和持续时间，可能导致暂时或永久的听觉阈值偏移（TTS、PTS）。最近的研究表明，前腹侧终球突触的突触功效恶化年龄相关性听力损失小鼠品系的耳蜗核（AVCN）。此外，还有一个功能减少突触后浓密神经元高频刺激的夹带。这些变化是可能是由于传入听觉神经纤维的活动减弱所致。另一方面，噪音侮辱，在听觉神经中产生反复的短期过度活跃。过度的兴奋可能会导致对末球突触及其突触后目标产生有害影响。因为 AVCN 提供了重要的线索对于声音定位和语音识别的高级听觉中心来说，了解噪声引起的听力损失在第一个中继突触的功能后果。因此，我们建议2 具体目标。在第一个目标中，我们将明确检验末球突触功效的假设接触噪声后，终端立即受损。然而，适度恢复疗效损伤仅导致 TTS，而 NIHL 伴有 PTS 时疗效会永久降低。我们将利用近交 CBA 小鼠噪声暴露结果的低个体差异。使用改良全耳蜗核切片制备，我们将探讨突触传递的几个方面噪声过度暴露后的电生理记录。在第二个目标中，我们将检验假设噪声引起的听力损失会影响突触后丛中的低阈值 K+ 电导 (lLr) 神经元；这种效应反过来又降低了这些神经元的时间编码能力。我们将表征诱导 NIHL 后从浓密细胞中提取 r，并通过激活听觉神经纤维在切片中具有真实的泊松分布尖峰序列。该项目的数据将补充和增强有关噪声引起的听力损失的周围效应。最终我们想解决的是 NIHL 后可以通过药物或设备干预来保留中枢听觉通路，因为中枢神经系统功能完整性是成功的听力损失后干预的重要组成部分。