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: 7383815
• 负责人: YONG WANG
• 金额: $ 7.26万
• 依托单位: UNIVERSITY OF UTAH
• 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/7383815
• 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

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1000万美国人患有噪声性听力损失（NIHL）。短期和长期噪音 在某些“正常”的工作和生活环境中，接触是一种主要的危险。噪声暴露，取决于 在强度和持续时间上，可导致暂时性或永久性听阈移位（TTS，PTS）。最近 研究表明，在前腹侧的球内突触处， 耳蜗核（AVCN）在一个品系的小鼠与年龄相关的听力损失。此外，还有一个功能 减少突触后神经元对高频刺激的夹带。这些变化是 可能是由于传入听觉神经纤维的活动减弱。另一方面，噪音的侮辱， 在听觉神经中产生反复出现的短期过度活跃。过度兴奋可能 对球内突触及其突触后靶点的有害作用。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，理解 在第一个中继突触处，噪声引起的听力损失的功能后果。因此，我们建议2 具体目标。在第一个目标中，我们将明确地测试这一假设，即突触效能在endbulb 终端在噪声暴露后立即受损。然而，疗效恢复与中度 损伤仅导致TTS，而在具有PTS的NIHL中，功效变得永久性降低。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 改良全耳蜗核切片制备，我们将探讨突触传递的几个方面 在噪声过度刺激后进行电生理记录。在第二个目标中，我们将测试假设 噪声引起的听力损失影响突触后丛的低阈值K+电导（ILr）， 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。我们将描述 在诱导NIHL后，从丛状细胞中提取r-mRNA，并通过激活神经元来测试丛状细胞的精细时间编码。 听觉神经纤维的切片中具有真实的泊松分布的尖峰序列。 该项目的数据将补充和加强有关 噪声性听力损失的周边效应。最后，我们要解决的问题是， 在NIHL后，通过药物或器械干预可以保留中枢听觉通路，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。