Short-Term Depression of Axonal Spikes at the Mouse Hippocampal Mossy Fibers and Sodium Channel-Dependent Modulation.
Short-Term Depression of Axonal Spikes at the Mouse Hippocampal Mossy Fibers and Sodium Channel-Dependent Modulation.
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DOI：
10.1523/eneuro.0415-17.2018
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发表时间：
2018-01
期刊：
影响因子：
3.4
通讯作者：
Kamiya H
中科院分区：
文献类型：
--
作者：
Ohura S;Kamiya H
轴突突是递质释放的重要上游过程，直接影响突触前末端的释放概率。尽管具有重要的功能意义，但轴突尖峰可能的活动依赖性调节尚未得到广泛研究，部分原因是由于电生理记录无法接近轴突的小结构。在这项研究中，我们测试了海马苔藓纤维轴突尖峰的使用依赖性变化的可能性，在那里从轴突终端直接记录是很容易实现的。分别对雌雄小鼠的海马切片，并从CA3区透明层中视觉识别的巨大苔藓纤维钮扣中获得松片钳记录。对齿状回颗粒细胞层的刺激在单个钮扣处引起轴突尖峰，这种尖峰以完全或不发生的方式发生。出乎意料的是，在50毫秒的时间间隔内，对配对刺激的第二个尖峰的峰值幅度比第一个尖峰略小，但可重复。在训练过程中，20或100赫兹的重复刺激也会引起进行性使用依赖性抑郁。值得注意的是，缬曲定，一种钠通道失活抑制剂，显著加速了抑制，对初始峰值的影响最小。这些结果表明，钠通道有助于海马苔藓纤维轴突尖峰的使用依赖性抑制，可能是通过塑造轴突尖峰后的后去极化（ADP）。ADP期间长时间的去极化可能使部分钠通道失活，从而抑制海马苔藓纤维的后续峰值。
Axonal spike is an important upstream process of transmitter release, which directly impacts on release probability from the presynaptic terminals. Despite the functional significance, possible activity-dependent modulation of axonal spikes has not been studied extensively, partly due to inaccessibility of the small structures of axons for electrophysiological recordings. In this study, we tested the possibility of use-dependent changes in axonal spikes at the hippocampal mossy fibers, where direct recordings from the axon terminals are readily feasible. Hippocampal slices were made from mice of either sex, and loose-patch clamp recordings were obtained from the visually identified giant mossy fiber boutons located in the stratum lucidum of the CA3 region. Stimulation of the granule cell layer of the dentate gyrus elicited axonal spikes at the single bouton which occurred in all or none fashion. Unexpected from the digital nature of spike signaling, the peak amplitude of the second spikes in response to paired stimuli at a 50-ms interval was slightly but reproducibly smaller than the first spikes. Repetitive stimuli at 20 or 100 Hz also caused progressive use-dependent depression during the train. Notably, veratridine, an inhibitor of inactivation of sodium channels, significantly accelerated the depression with minimal effect on the initial spikes. These results suggest that sodium channels contribute to use-dependent depression of axonal spikes at the hippocampal mossy fibers, possibly by shaping the afterdepolarization (ADP) following axonal spikes. Prolonged depolarization during ADP may inactivate a fraction of sodium channels and thereby suppresses the subsequent spikes at the hippocampal mossy fibers.