RT Journal Article SR Electronic T1 Short-Term Depression of Axonal Spikes at the Mouse Hippocampal Mossy Fibers and Sodium Channel-Dependent Modulation JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0415-17.2018 DO 10.1523/ENEURO.0415-17.2018 A1 Shunsuke Ohura A1 Haruyuki Kamiya YR 2018 UL http://www.eneuro.org/content/early/2018/02/12/ENEURO.0415-17.2018.abstract AB 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 50 ms interval was slightly but reproducibly smaller than the first spikes. Repetitive stimuli at 20 Hz 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.Significance Statement Spike signaling along axons is thought to highly reliable digital process. In this study, we tested the possibility of analog tuning of axonal spikes using direct recordings from single hippocampal mossy fiber terminals. We found that axonal spikes are subject to robust use-dependent short-term depression. Notably, the application of veratridine, an inhibitor of inactivation of sodium channels, selectively accelerates short-term depression with minimal effect on the initial axonal spikes. These results illustrate the novel form of short-term plasticity of axonal spikes in single axon terminal levels, and suggest that slow activating sodium channels of persistent-type (INaP) or resurgent types (INaR), different from the transient-type (INaT) responsible for spike generation, might be involved in modulation of paired-pulse depression of axonal spikes.