Department of Neurobiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
eNeuro. 2018 Feb 20;5(1). doi: 10.1523/ENEURO.0415-17.2018. eCollection 2018 Jan-Feb.
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.
轴突峰是递质释放的一个重要上游过程，直接影响到突触前末梢的释放概率。尽管其功能意义重大，但由于轴突的小结构难以进行电生理记录，因此，对轴突峰的可能的活动依赖性调制尚未进行广泛研究。在这项研究中，我们测试了在海马苔藓纤维中轴突峰的使用依赖性变化的可能性，在那里可以方便地从轴突末梢进行直接记录。从雌雄小鼠制备海马切片，并从视觉上识别的 CA3 区层 lucidum 中的巨大苔藓纤维末梢获得松散的贴附式记录。刺激齿状回颗粒细胞层可在单个末梢引发轴突峰，其以全或无的方式发生。出乎意料的是，由于尖峰信号的数字性质，在 50ms 间隔的成对刺激下，第二个尖峰的峰值幅度略小于第一个尖峰，但可重现。在 20 或 100Hz 的重复刺激也会导致在训练过程中逐渐出现使用依赖性的抑制。值得注意的是，veratridine 是钠离子通道失活的抑制剂，它对初始尖峰的影响最小，但能显著加速抑制作用。这些结果表明，钠离子通道可能通过塑造轴突峰后的去极化（ADP）来参与海马苔藓纤维的使用依赖性抑制。ADP 期间的长时间去极化可能会使钠离子通道失活一部分，从而抑制海马苔藓纤维中的后续尖峰。
