Impaired auditory processing and altered structure of the endbulb of Held synapse in mice lacking the GluA3 subunit of AMPA receptors.
Impaired auditory processing and altered structure of the endbulb of Held synapse in mice lacking the GluA3 subunit of AMPA receptors.
复制标题
DOI：
10.1016/j.heares.2016.12.006
复制
发表时间：
2017-02
期刊：
影响因子：
2.8
通讯作者：
Rubio ME
中科院分区：
文献类型：
--
作者：
García-Hernández S;Abe M;Sakimura K;Rubio ME
AMPA谷氨酸受体复合物具有由GluA 3和GluA 4等亚基赋予的快速动力学，对于突触传递的时间精确性至关重要。GluA 3在听觉脑干听觉加工和经验相关变化中的具体作用尚不清楚。我们通过野生型（WT）和GluA 3基因敲除（GluA 3-KO）小鼠研究了GluA 3在听觉加工中的作用。用听性脑干反应（ABR）评价听功能，用电镜观察听神经丛细胞突触（AN-BC突触）的超微结构。由于GluA 3亚基的标记增加耳蜗核内的听觉神经突触在响应瞬态声音减少，我们研究了GluA 3在听觉处理中的经验依赖性变化的作用。我们通过堵塞一只耳朵诱导短暂的声音减少，并在WT和GluA 3-KO小鼠中评估了去除耳塞后长达60天的ABR阈值和峰值振幅恢复。我们发现GluA 3的缺失导致听觉信号传导受损，这反映在ABR峰值振幅降低、峰值2的延迟增加、早发性听力损失以及AN-BC突触的突触后密度（PSD）的数量和大小减少。此外，GluA 3的缺乏阻碍了短暂性耳塞后ABR阈值的恢复。我们的结论是，GluA 3是所需的正常听觉信号，正常的超微结构的AN-BC突触在耳蜗核和正常的经验依赖性的变化，在听觉处理后，短暂的声音减少。
AMPA glutamate receptor complexes with fast kinetics conferred by subunits like GluA3 and GluA4 are essential for temporal precision of synaptic transmission. The specific role of GluA3 in auditory processing and experience related changes in the auditory brainstem remain unknown. We investigated the role of the GluA3 in auditory processing by using wild type (WT) and GluA3 knockout (GluA3-KO) mice. We recorded auditory brainstem responses (ABR) to assess auditory function and used electron microscopy to evaluate the ultrastructure of the auditory nerve synapse on bushy cells (AN-BC synapse). Since labeling for GluA3 subunit increases on auditory nerve synapses within the cochlear nucleus in response to transient sound reduction, we investigated the role of GluA3 in experience-dependent changes in auditory processing. We induced transient sound reduction by plugging one ear and evaluated ABR threshold and peak amplitude recovery for up to 60 days after ear plug removal in WT and GluA3-KO mice. We found that the deletion of GluA3 leads to impaired auditory signaling that is reflected in decreased ABR peak amplitudes, an increased latency of peak 2, early onset hearing loss and reduced numbers and sizes of postsynaptic densities (PSDs) of AN-BC synapses. Additionally, the lack of GluA3 hampers ABR threshold recovery after transient ear plugging. We conclude that GluA3 is required for normal auditory signaling, normal ultrastructure of AN-BC synapses in the cochlear nucleus and normal experience-dependent changes in auditory processing after transient sound reduction.