Department of Otolaryngology and Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114.
Department of Otolaryngology and Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114
J Neurosci. 2018 Aug 8;38(32):7108-7119. doi: 10.1523/JNEUROSCI.3240-17.2018. Epub 2018 Jul 5.
Aging listeners, even in the absence of overt hearing loss measured as changes in hearing thresholds, often experience impairments processing temporally complex sounds such as speech in noise. Recent evidence has shown that normal aging is accompanied by a progressive loss of synapses between inner hair cells and auditory nerve fibers. The role of this cochlear synaptopathy in degraded temporal processing with age is not yet understood. Here, we used population envelope following responses, along with other hair cell- and neural-based measures from an age-graded series of male and female CBA/CaJ mice to study changes in encoding stimulus envelopes. By comparing responses obtained before and after the application of the neurotoxin ouabain to the inner ear, we demonstrate that we can study changes in temporal processing on either side of the cochlear synapse. Results show that deficits in neural coding with age emerge at the earliest neural stages of auditory processing and are correlated with the degree of cochlear synaptopathy. These changes are seen before losses in neural thresholds and particularly affect the suprathreshold processing of sound. Responses obtained from more central sources show smaller differences with age, suggesting compensatory gain. These results show that progressive cochlear synaptopathy is accompanied by deficits in temporal coding at the earliest neural generators and contribute to the suprathreshold sound processing deficits observed with age. Aging listeners often experience difficulty hearing and understanding speech in noisy conditions. The results described here suggest that age-related loss of cochlear synapses may be a significant contributor to those performance declines. We observed aberrant neural coding of sounds in the early auditory pathway, which was accompanied by and correlated with an age-progressive loss of synapses between the inner hair cells and the auditory nerve. Deficits first appeared before changes in hearing thresholds and were largest at higher sound levels relevant to real world communication. The noninvasive tests described here may be adapted to detect cochlear synaptopathy in the clinical setting.
随着年龄的增长，即使没有明显的听力损失（表现在听力阈值的变化上），听力听众在处理复杂的时间声音（如噪声中的语音）时也经常会遇到障碍。最近的证据表明，正常衰老伴随着内毛细胞和听神经纤维之间突触的逐渐丧失。这种耳蜗突触病在年龄相关的时间处理能力下降中的作用尚不清楚。在这里，我们使用群体包络跟随反应，以及来自一系列年龄分级的雄性和雌性 CBA/CaJ 小鼠的基于毛细胞和神经的其他测量方法，研究刺激包络的编码变化。通过比较在内耳应用神经毒素哇巴因前后获得的反应，我们证明我们可以研究耳蜗突触两侧的时间处理变化。结果表明，随着年龄的增长，神经编码的缺陷出现在听觉处理的最早神经阶段，并且与耳蜗突触病的程度相关。这些变化在神经阈值损失之前出现，特别是影响声音的阈上处理。从中枢源获得的反应显示出与年龄相关的较小差异，表明补偿增益。这些结果表明，进行性耳蜗突触病伴随着最早的神经发生器中的时间编码缺陷，并导致与年龄相关的阈上声音处理缺陷。随着年龄的增长，听力听众经常难以在嘈杂环境中听到和理解言语。这里描述的结果表明，耳蜗突触的年龄相关性丧失可能是这些表现下降的重要原因。我们观察到早期听觉通路中声音的异常神经编码，这种编码伴随着并与内毛细胞和听神经之间的突触进行性丧失相关。缺陷首先出现在听力阈值变化之前，并且在与现实世界交流相关的更高声音水平上最大。这里描述的非侵入性测试可以适应于在临床环境中检测耳蜗突触病。
