Abstract：
Cochlear synaptopathy is the noise-induced or age-related loss of ribbon synapses between inner hair cells (IHCs) and auditory-nerve fibers (ANFs), first reported in CBA/CaJ mice. Recordings from single ANFs in anesthetized, noise-exposed guinea pigs suggested that neurons with low spontaneous rates (SRs) and high thresholds are more vulnerable than low-threshold, high-SR fibers. However, there is extensive postexposure regeneration of ANFs in guinea pigs but not in mice. Here, we exposed CBA/CaJ mice to octave-band noise and recorded sound-evoked and spontaneous activity from single ANFs at least 2 wk later. Confocal analysis of cochleae immunostained for pre- and postsynaptic markers confirmed the expected loss of 40%-50% of ANF synapses in the basal half of the cochlea; however, our data were not consistent with a selective loss of low-SR fibers. Rather they suggested a loss of both SR groups in synaptopathic regions. Single-fiber thresholds and frequency tuning recovered to pre-exposure levels; however, response to tone bursts showed increased peak and steady-state firing rates, as well as decreased jitter in first-spike latencies. This apparent gain-of-function increased the robustness of tone-burst responses in the presence of continuous masking noise. This study suggests that the nature of noise-induced synaptic damage varies between different species and that, in mouse, the noise-induced hyperexcitability seen in central auditory circuits is also observed at the level of the auditory nerve.NEW & NOTEWORTHY Noise-induced damage to synapses between inner hair cells and auditory-nerve fibers (ANFs) can occur without permanent hair cell damage, resulting in pathophysiology that \"hides\" behind normal thresholds. Prior single-fiber neurophysiology in guinea pig suggested that noise selectively targets high-threshold ANFs. Here, we show that the lingering pathophysiology differs in mouse, with both ANF groups affected and a paradoxical gain-of-function in surviving low-threshold fibers, including increased onset rate, decreased onset jitter, and reduced maskability.
摘要：
耳蜗突触病是内部毛细胞（IHC）和听觉神经纤维（ANF）之间的带状突触的噪声诱导或年龄相关的损失，首次在CBA/CaJ小鼠中报道。麻醉的单个ANF的记录，噪声暴露的豚鼠表明，具有低自发率（SR）和高阈值的神经元比低阈值更脆弱，高SR纤维。然而,有广泛的暴露后再生的ANF在豚鼠，而不是在小鼠。这里,我们将CBA/CaJ小鼠暴露于倍频程噪声中，并在至少2周后记录了单个ANF的声音诱发和自发活动。对突触前和突触后标记物进行免疫染色的耳蜗共聚焦分析证实，在耳蜗的基底一半中，ANF突触的预期损失40％-50％；但是，我们的数据与低SR光纤的选择性损耗不一致.相反，他们建议突触病变区域的两个SR基团都丢失。单光纤阈值和频率调谐恢复到暴露前水平；然而，对音调突发的反应显示峰值和稳态激发率增加，以及减少第一尖峰延迟中的抖动。在存在连续掩蔽噪声的情况下，这种明显的功能增益增加了音调突发响应的鲁棒性。这项研究表明，噪声引起的突触损伤的性质在不同物种之间有所不同，在老鼠身上,在中央听觉回路中观察到的噪声引起的兴奋过度也在听觉神经水平上观察到。噪声引起的内毛细胞和听觉神经纤维（ANF）之间的突触损伤可以在没有永久性毛细胞损伤的情况下发生，导致病理生理学“隐藏”在正常阈值后面。豚鼠先前的单纤维神经生理学表明，噪声选择性地靶向高阈值ANF。这里,我们表明，小鼠的持久病理生理学不同，由于两个ANF组都受到影响，并且在存活的低阈值纤维中具有自相矛盾的功能增益，包括发作率增加，减少的起始抖动，降低了可遮盖性。
