O'Neil Jahn N, Limb Charles J, Baker Christa A, Ryugo David K
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
J Comp Neurol. 2010 Jun 15;518(12):2382-404. doi: 10.1002/cne.22339.
Congenital deafness results in synaptic abnormalities in auditory nerve endings. These abnormalities are most prominent in terminals called endbulbs of Held, which are large, axosomatic synaptic endings whose size and evolutionary conservation emphasize their importance. Transmission jitter, delay, or failures, which would corrupt the processing of timing information, are possible consequences of the perturbations at this synaptic junction. We sought to determine whether electrical stimulation of the congenitally deaf auditory system via cochlear implants would restore the endbulb synapses to their normal morphology. Three and 6-month-old congenitally deaf cats received unilateral cochlear implants and were stimulated for a period of 10-19 weeks by using human speech processors. Implanted cats exhibited acoustic startle responses and were trained to approach their food dish in response to a specific acoustic stimulus. Endbulb synapses were examined by using serial section electron microscopy from cohorts of cats with normal hearing, congenital deafness, or congenital deafness with a cochlear implant. Synapse restoration was evident in endbulb synapses on the stimulated side of cats implanted at 3 months of age but not at 6 months. In the young implanted cats, postsynaptic densities exhibited normal size, shape, and distribution, and synaptic vesicles had density values typical of hearing cats. Synapses of the contralateral auditory nerve in early implanted cats also exhibited synapses with more normal structural features. These results demonstrate that electrical stimulation with a cochlear implant can help preserve central auditory synapses through direct and indirect pathways in an age-dependent fashion.
先天性耳聋会导致听神经末梢出现突触异常。这些异常在被称为 Held 终球的终末最为显著，Held 终球是大型的轴体突触终末，其大小和进化保守性凸显了它们的重要性。传递抖动、延迟或失败会破坏时间信息的处理，而这些都可能是此突触连接扰动的后果。我们试图确定通过人工耳蜗对先天性耳聋的听觉系统进行电刺激是否能使终球突触恢复到正常形态。3 个月和 6 个月大的先天性耳聋猫接受了单侧人工耳蜗植入，并使用人类言语处理器进行了 10 - 19 周的刺激。植入人工耳蜗的猫表现出听觉惊吓反应，并经过训练能对特定听觉刺激做出反应，接近它们的食盘。通过对听力正常、先天性耳聋或植入人工耳蜗的先天性耳聋猫群进行连续切片电子显微镜检查来观察终球突触。在 3 个月大时植入人工耳蜗的猫的受刺激侧的终球突触中，突触恢复明显，但 6 个月大时植入的猫则不然。在幼年植入人工耳蜗的猫中，突触后致密物呈现出正常的大小、形状和分布，并且突触小泡具有听力正常的猫典型的密度值。早期植入人工耳蜗的猫的对侧听神经突触也表现出结构特征更正常的突触。这些结果表明，人工耳蜗电刺激可以通过直接和间接途径以年龄依赖的方式帮助保留中枢听觉突触。
