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1000万美国人遭受噪音造成听力损失（NIHL）。短期和长期噪音 在某些“正常”工作和生活环境中，暴露是一个主要危害。噪音暴露，具体取决于 在强度和持续时间上，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，突触功效在腹侧末端突触处恶化 与年龄相关的听力损失的小鼠菌株中的耳蜗核（AVCN）。此外，还有一个功能 减少了突触后灌注神经元中高频刺激的夹带。这些变化是 可能是由于传入的听觉神经纤维的活性减少所致。另一方面，噪音侮辱 在听觉神经中产生反复出现的短期多动症。过度的激发可能会有 对末端突触及其突触后目标的有害作用。因为AVCN提供了重要的提示 对于更高的听觉中心以进行声音本地化和语音识别，必须了解 噪声引起的功能后果在第一个继电器突触中引起听力损失。因此，我们提出2 具体目标。在第一个目标中，我们将明确检验末端突触功效的假设 噪声暴露后立即损坏终端。但是，功效以中等 仅导致TTS的侮辱，而PTS中NIHL的功效将永久降低。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 修改了整个耳蜗核切片准备，我们将探测突触传播的几个方面 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灌木后的低阈值K+电导（LLR） 神经元；这种效果反过来降低了这些神经元中的时间编码能力。我们将表征 诱导NIHL后的Rfrom浓密细胞，并通过激活浓密的细胞测试细胞的精细时间编码 带有逼真的泊松的听觉神经纤维在切片中分发了尖峰火车。 该项目的数据将补充并增强有关该项目的现有信息 噪声引起的听力损失的外围效应。最终，我们想解决的完整性是否 NIHL之后，可以通过药物或装置干预来保留中央听觉途径，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。