Biophysical and morphological changes in inner hair cells and their efferent innervation in the ageing mouse cochlea.
Biophysical and morphological changes in inner hair cells and their efferent innervation in the ageing mouse cochlea.
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DOI：
10.1113/jp280256
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发表时间：
2021-01
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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;Carlton AJ;Johnson SL;Brown SDM;Holley MC;Bowl MR;Marcotti W
内毛细胞(IHC)是哺乳动物耳蜗的主要感觉受体，它将声音信息转化为电信号，并传递给传入神经元。IHC的功能变化是与年龄相关的听力损失的潜在原因。在这里，我们研究了携带CDH23ah1等位基因的早发性听力损失小鼠(C57BL/6J和C57BL/6NTac)、晚发性听力损失小鼠(C3H/HeJ)以及听力中等表型的CDh23ah1突变校正小鼠(C57BL/6NTacCDh23+)的IHC的功能特征。至少15个月龄以前，9-12 kHz耳蜗区的IHC没有明显的丢失，但从6个月龄开始，其表面积逐渐减少30-40%。尽管BK电流的大小随着年龄的增长而减小，但IHC保持着正常的KCNQ4电流和静止膜电位。C57BL/6J和C57BL/6NTac的基底膜改变最严重，C57BL/6NTacCdh23+的改变较轻，C3H/HeJ小鼠的基底膜改变很小或不存在。我们还发现，外侧橄榄耳蜗区(LOC)的传出纤维改变了与老年IHC的功能性轴突-躯体联系，但这只在C3H/HeJ小鼠中零星可见。传出的突触后SK2通道出现在传出联系建立之前，提示IHC可能在重新建立LOC-IHC突触中起直接作用。最后，我们发现，在携带CDh23ah1等位基因的小鼠中，来自IHC的机电换能器(MET)电流的大小随着年龄的增长而显著减小，但在C57BL/6NTacCDh23+小鼠中则不明显，这表明MET装置直接参与了年龄相关性听力损失的进展。
Inner hair cells (IHCs) are the primary sensory receptors of the mammalian cochlea, transducing acoustic information into electrical signals that are relayed to the afferent neurons. Functional changes in IHCs are a potential cause of age-related hearing loss. Here, we have investigated the functional characteristics of IHCs from early-onset hearing loss mice harbouring the allele Cdh23ahl (C57BL/6J and C57BL/6NTac), from late-onset hearing loss mice (C3H/HeJ), and from mice corrected for the Cdh23ahl mutation (C57BL/6NTacCdh23+) with an intermediate hearing phenotype. There was no significant loss of IHCs in the 9-12 kHz cochlear region up to at least 15 months of age, but their surface area decreased progressively by 30-40% starting from ~6 months of age. Although the size of the BK current decreased with age, IHCs retained a normal KCNQ4 current and resting membrane potential. These basolateral membrane changes were most severe for C57BL/6J and C57BL/6NTac, less so for C57BL/6NTacCdh23+ and minimal or absent in C3H/HeJ mice. We also found that lateral olivocochlear (LOC) efferent fibres reform functional axon-somatic connections with aged IHCs, but this was seen only sporadically in C3H/HeJ mice. The efferent post-synaptic SK2 channels appear prior to the establishment of the efferent contacts, suggesting that IHCs may play a direct role in re-establishing the LOC-IHC synapses. Finally, we showed that the size of the mechanoelectrical transducer (MET) current from IHCs decreased significantly with age in mice harbouring the Cdh23ahl allele but not in C57BL/6NTacCdh23+mice, indicating that the MET apparatus directly contributes to the progression of age-related hearing loss.