Department of Neuroscience, University of Connecticut Health, Farmington, CT, United States of America.
The Connecticut Institute for the Brain and Cognitive Sciences (IBACS), Storrs, CT, United States of America.
PLoS One. 2021 May 12;16(5):e0251412. doi: 10.1371/journal.pone.0251412. eCollection 2021.
Hearing depends on the transduction of sounds into neural signals by the inner hair cells of the cochlea. Cochleae also have outer hair cells with unique electromotile properties that increase auditory sensitivity, but they are particularly susceptible to damage by intense noise exposure, ototoxic drugs, and aging. Although the outer hair cells have synapses on afferent neurons that project to the brain, the function of this neuronal circuit is unclear. Here, we created a novel mouse allele that inserts a fluorescent reporter at the C1ql1 locus which revealed gene expression in the outer hair cells and allowed creation of outer hair cell-specific C1ql1 knockout mice. We found that C1ql1 expression in outer hair cells corresponds to areas with the most sensitive frequencies of the mouse audiogram, and that it has an unexpected adolescence-onset developmental timing. No expression was observed in the inner hair cells. Since C1QL1 in the brain is made by neurons, transported anterogradely in axons, and functions in the synaptic cleft, C1QL1 may serve a similar function at the outer hair cell afferent synapse. Histological analyses revealed that C1ql1 conditional knockout cochleae may have reduced outer hair cell afferent synapse maintenance. However, auditory behavioral and physiological assays did not reveal a compelling phenotype. Nonetheless, this study identifies a potentially useful gene expressed in the cochlea and opens the door for future studies aimed at elucidating the function of C1QL1 and the function of the outer hair cell and its afferent neurons.
听力依赖于耳蜗内毛细胞将声音转化为神经信号。耳蜗中的外毛细胞具有独特的电运动特性，可以提高听觉敏感度，但它们特别容易受到强噪声暴露、耳毒性药物和衰老的损害。尽管外毛细胞在外周传入神经元上有突触，这些神经元投射到大脑，但这个神经元回路的功能尚不清楚。在这里，我们创建了一个新的小鼠等位基因，该基因在 C1ql1 基因座插入一个荧光报告基因，在外毛细胞中显示基因表达，并允许创建外毛细胞特异性 C1ql1 敲除小鼠。我们发现，外毛细胞中的 C1ql1 表达与小鼠听力图中最敏感频率的区域相对应，并且它具有出乎意料的青春期起始发育时间。在内毛细胞中没有观察到表达。由于大脑中的 C1QL1 是由神经元产生的，沿轴突顺行运输，并在突触间隙中发挥作用，因此 C1QL1 在外毛细胞传入突触处可能具有类似的功能。组织学分析显示，C1ql1 条件性敲除耳蜗可能减少了外毛细胞传入突触的维持。然而，听觉行为和生理测定并未揭示出引人注目的表型。尽管如此，这项研究确定了一种在耳蜗中表达的潜在有用基因，并为未来旨在阐明 C1QL1 功能以及外毛细胞和其传入神经元功能的研究开辟了道路。
