Pathophysiological changes in inner hair cell ribbon synapses in the ageing mammalian cochlea.
Pathophysiological changes in inner hair cell ribbon synapses in the ageing mammalian cochlea.
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DOI：
10.1113/jp280018
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发表时间：
2020-10
期刊：
影响因子：
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通讯作者：
Marcotti W
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文献类型：
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作者：
Jeng JY;Ceriani F;Olt J;Brown SDM;Holley MC;Bowl MR;Johnson SL;Marcotti W
哺乳动物耳蜗内毛细胞（IHC）是能够提供声音信号动态编码的专门感觉受体。这种能力在很大程度上是由它们的带状突触赋予的，带状突触在IHC的突触前活动区束缚了大量的囊泡，允许高速率的持续突触传递到传入纤维上。带状突触的生理学和形态学特性如何随年龄而变化，在很大程度上仍然是未知的。在这里，我们研究了在听力研究中常用的四种小鼠品系的老化耳蜗（9-12 kHz区域）中IHC带状突触的生物物理和形态学特性：早发性进行性听力损失（C57 BL/6 J和C57 BL/6 NTac）和“良好听力”品系（C57 BL/6 NTacCdh 23+和C3 H/HeJ）。我们发现，随着年龄的增长，无论是蜗轴和柱侧的IHC表现出损失的丝带，但增加的体积仍然存在。这些仅在6个月龄后发生的形态学变化与不同小鼠品系的听力损失水平相关，C57 BL/6 NTac和C57 BL/6 J最严重，C57 BL/6 NTacCdh 23+较轻，C3 H/HeJ品系不存在。尽管年龄相关的丝带数量减少，在四个菌株中的三个，Ca 2+依赖性胞吐的大小和动力学，以及突触囊泡的补充，在IHC中没有受到影响。囊泡释放的程度在更少，但更大的，个别剩余的带状突触与突触后传入神经末梢共定位可能会增加，这表明存在一个以前未知的程度的功能补偿在老化的小鼠耳蜗。年龄相关性听力损失外毛细胞内毛细胞出生后日螺旋神经节神经元细胞膜电容机械电传导听觉脑干反应
Mammalian cochlear inner hair cells (IHCs) are specialized sensory receptors able to provide dynamic coding of sound signals. This ability is largely conferred by their ribbon synapses, which tether a large number of vesicles at the IHC’s presynaptic active zones, allowing high rates of sustained synaptic transmission onto the afferent fibres. How the physiological and morphological properties of ribbon synapses change with age is still largely unknown. Here, we have investigated the biophysical and morphological properties of IHC ribbon synapses in the ageing cochlea (9-12 kHz region) of four mouse strains commonly used in hearing research: early-onset progressive hearing loss (C57BL/6J and C57BL/6NTac) and “good hearing” strains (C57BL/6NTacCdh23+ and C3H/HeJ). We found that with age, both modiolar and pillar sides of the IHC exhibited a loss of ribbons, but an increased volume of those that remained. These morphological changes, which only occurred after 6 months of age, were correlated with the level of hearing loss in the different mouse strains, being most severe for C57BL/6NTac and C57BL/6J, less so for C57BL/6NTacCdh23+ and absent in C3H/HeJ strains. Despite the age-related reduction in ribbon number in three out of four strains, the size and kinetics of Ca2+-dependent exocytosis, as well as the replenishment of synaptic vesicles, in IHCs was not affected. The degree of vesicle release at the fewer, but larger, individual remaining ribbon synapses colocalized with the post-synaptic afferent terminals is likely to increase, indicating the presence of a previously unknown degree of functional compensation in the ageing mouse cochlea. age-related hearing loss outer hair cells inner hair cells postnatal day spiral ganglion neuron cell membrane capacitance mechanoelectrical transduction auditory brainstem response