Karagulyan Nare, Thirumalai Anupriya, Michanski Susann, Qi Yumeng, Fang Qinghua, Wang Haoyu, Ortner Nadine J, Striessnig Jörg, Strenzke Nicola, Wichmann Carolin, Hua Yunfeng, Moser Tobias
Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany.
Auditory Neuroscience & Synaptic Nanophysiology Group, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Sci Adv. 2025 Jun 20;11(25):eadu7898. doi: 10.1126/sciadv.adu7898. Epub 2025 Jun 18.
Our sense of hearing processes sound intensities spanning six orders of magnitude. In the ear, the receptor potential of presynaptic inner hair cells (IHCs) covers the entire intensity range, while postsynaptic spiral ganglion neurons (SGNs) tile the range with their firing rate codes. IHCs vary the voltage dependence of Ca channel activation among their active zones (AZs), potentially diversifying SGN firing. Here, we tested this hypothesis in mice modeling the human Ca1.3 mutation that causes low-voltage Ca channel activation. We demonstrate activation of Ca influx and glutamate release of IHC AZs at lower voltages, increased spontaneous firing in SGNs, and lower sound threshold of Ca1.3 mice. Loss of synaptic ribbons in IHCs at ambient sound levels of mouse husbandry indicates that low-voltage Ca channel activation poses a risk for noise-induced synaptic damage. We propose that the heterogeneous voltage dependence of Ca1.3 activation among presynaptic IHC AZs contributes to the diversity of firing among the postsynaptic SGNs.
我们的听觉系统能够处理跨越六个数量级的声音强度。在耳朵中,突触前内毛细胞(IHC)的感受器电位覆盖了整个强度范围,而突触后螺旋神经节神经元(SGN)则通过其放电率编码来划分该范围。IHC在其活性区(AZ)之间改变钙通道激活的电压依赖性,这可能使SGN放电多样化。在这里,我们在模拟导致低电压钙通道激活的人类Ca1.3突变的小鼠中测试了这一假设。我们证明了在较低电压下IHC AZ的钙内流激活和谷氨酸释放,SGN中自发放电增加,以及Ca1.3小鼠的声音阈值降低。在小鼠饲养环境声音水平下,IHC中突触小带的丧失表明低电压钙通道激活对噪声诱导的突触损伤构成风险。我们提出,突触前IHC AZ之间Ca1.3激活的异质电压依赖性有助于突触后SGN之间放电的多样性。
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