AUTHOR=Kamiya Haruyuki TITLE=Modeling Analysis of Axonal After Potential at Hippocampal Mossy Fibers JOURNAL=Frontiers in Cellular Neuroscience VOLUME=13 YEAR=2019 URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2019.00210 DOI=10.3389/fncel.2019.00210 ISSN=1662-5102 ABSTRACT=

Action potentials reliably propagate along the axons, and after potential often follows the axonal action potentials. After potential lasts for several tens of millisecond and plays a crucial role in regulating excitability during repetitive firings of the axon. Several mechanisms underlying the generation of after potential have been suggested, including activation of ionotropic autoreceptors, accumulation of K+ ions in the surrounding extracellular space, the opening of slow voltage-dependent currents, and capacitive discharge of upstream action potentials passively propagated through axon cable. Among them, capacitive discharge is difficult to examine experimentally, since the quantitative evaluation of a capacitive component requires simultaneous recordings from at least two different sites on the connecting axon. In this study, a series of numerical simulation of the axonal action potential was performed using a proposed model of the hippocampal mossy fiber where morphological as well as electrophysiological data are accumulated. To evaluate the relative contribution of the capacitive discharge in axonal after potential, voltage-dependent Na+ current as well as voltage-dependent K+ current was omitted from a distal part of mossy fiber axons. Slow depolarization with a similar time course with the recorded after potential in the previous study was left after blockade of Na+ and K+ currents, suggesting that a capacitive component contributes substantially in axonal after potential following propagating action potentials. On the other hand, it has been shown that experimentally recorded after potential often showed clear voltage-dependency upon changes in the initial membrane potential, obviously deviating from voltage-independent nature of the capacitive component. The simulation revealed that activation of voltage-dependent K+ current also contributes to shape a characteristic waveform of axonal after potential and reconstitute similar voltage-dependency with that reported for the after potential recorded from mossy fiber terminals. These findings suggest that the capacitive component reflecting passive propagation of upstream action potential substantially contributes to the slow time course of axonal after potential, although voltage-dependent K+ current provided a characteristic voltage dependency of after potential waveform.