PDF(Pubmed)
Abstract：
Loss of synapses between spiral ganglion neurons and inner hair cells (IHC synaptopathy) leads to an auditory neuropathy called hidden hearing loss (HHL) characterized by normal auditory thresholds but reduced amplitude of sound-evoked auditory potentials. It has been proposed that synaptopathy and HHL result in poor performance in challenging hearing tasks despite a normal audiogram. However, this has only been tested in animals after exposure to noise or ototoxic drugs, which can cause deficits beyond synaptopathy. Furthermore, the impact of supernumerary synapses on auditory processing has not been evaluated. Here, we studied mice in which IHC synapse counts were increased or decreased by altering neurotrophin 3 (Ntf3) expression in IHC supporting cells. As we previously showed, postnatal Ntf3 knockdown or overexpression reduces or increases, respectively, IHC synapse density and suprathreshold amplitude of sound-evoked auditory potentials without changing cochlear thresholds. We now show that IHC synapse density does not influence the magnitude of the acoustic startle reflex or its prepulse inhibition. In contrast, gap-prepulse inhibition, a behavioral test for auditory temporal processing, is reduced or enhanced according to Ntf3 expression levels. These results indicate that IHC synaptopathy causes temporal processing deficits predicted in HHL. Furthermore, the improvement in temporal acuity achieved by increasing Ntf3 expression and synapse density suggests a therapeutic strategy for improving hearing in noise for individuals with synaptopathy of various etiologies.
摘要：
螺旋神经节神经元和内毛细胞之间的突触丢失（IHC突触病）导致称为隐性听力损失（HHL）的听觉神经病变，其特征在于正常的听觉阈值，但声音诱发的听觉电位的幅度降低。有人提出，尽管听力图正常，但突触疗法和HHL在具有挑战性的听力任务中的表现不佳。然而,这只在暴露于噪音或耳毒性药物后的动物中进行了测试，这可能导致突触之外的缺陷。此外，尚未评估过数突触对听觉处理的影响。这里,我们研究了通过改变IHC支持细胞中神经营养蛋白3(Ntf3)的表达而增加或减少IHC突触计数的小鼠.正如我们之前所展示的,出生后Ntf3敲低或过表达减少或增加，分别,在不改变耳蜗阈值的情况下，声音诱发听觉电位的IHC突触密度和阈值幅度。我们现在表明，IHC突触密度不会影响声惊吓反射或其脉冲前抑制的幅度。相比之下,间隙前脉冲抑制，听觉时间处理的行为测试，根据Ntf3表达水平降低或增强。这些结果表明IHC突触病会导致HHL中预测的时间处理缺陷。此外，通过增加Ntf3表达和突触密度实现的时间敏锐度改善提示了一种治疗策略，可以改善患有各种病因的突触病的个体的噪声听力。
