Effect of Noise Induced Hearing Loss on AVCN Principal Neurons

超过1000万美国人患有噪声性听力损失(NIHL)。短期和长期噪声 在某些“正常”的工作和生活环境中，暴露是一种主要危险。噪声暴露，视情况而定 在强度和持续时间上，可导致暂时性或永久性听阈偏移(TTS，PTS)。近期 研究表明，在前腹侧的终球突触处，突触的效能降低。 老年性听力损失小鼠的耳蜗核(AVCN)。此外，还有一个功能性的 减少突触后丛状神经元对高频刺激的缠绕。这些变化是 可能是由于传入听神经纤维活动减弱所致。另一方面，噪音侮辱， 在听神经中产生反复出现的短期多动症。过度兴奋可能会导致 对内球突触及其突触后靶点的不利影响。因为AVCN提供了重要的线索 对于用于声音定位和语音识别的高级听觉中枢，理解 噪声性听力损失在第一个中继性突触的功能后果。因此，我们建议2 明确的目标。在第一个目标中，我们将明确地检验这样一个假设，即突触在终球的功效 噪声暴露后，端子会立即受损。然而，疗效恢复为中度 侮辱只会导致TTS，而在伴有PTS的NIHL中，疗效会永久降低。我们会 利用近交系CBA小鼠噪声暴露结果的低个体变异性。使用 改良的全耳蜗核切片制备，我们将探讨突触传递的几个方面 以及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 噪声性听力损失对突触后丛区低阈值K+电导的影响 神经元；这种效应反过来降低了这些神经元的时间编码能力。我们将描述 从诱导NIHL后的丛生细胞中分离出来，并通过激活 听神经纤维与真实泊松分布的棘波串在切片上。 该项目的数据将补充和加强现有的关于 噪声性听力损失的外周效应。最终，我们想要解决的是 中枢听觉通路在NIHL后可通过药物或药物干预得到保护，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。

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.