The Slow Depolarization Following Individual Spikes in Thin, Unmyelinated Axons in Mammalian Cortex

Morten Raastad

doi:10.3389/fncel.2019.00203

Abstract

An important goal in neuroscience is to understand how neuronal excitability is controlled. Therefore, Gardner-Medwin's 1972 discovery, that cerebellar parallel fibers were more excitable up to 100 ms after individual action potentials, could have had great impact. If this long-lasting effect were due to intrinsic membrane mechanisms causing a depolarizing after-potential (DAP) this was an important finding. However, that hypothesis met resistance because the use of K+ sensitive electrodes showed that synchronous activation, as commonly used in excitability tests, increased extracellular K+ concentration sufficiently to explain much of the hyperexcitability. It is still controversial because intra-axonal recordings, which could have settled the debate, have not been made from parallel fibers or other axons of similar calibers. If it had not been for the fact that such thin axons are, by far, the most common axon type in cortical areas and control almost all glutamate release, it would be tempting to ignore them until an appropriate intra-axonal recording technique is invented. I will go through the literature that, taken together, supports the hypothesis that a DAP is an intrinsic membrane mechanism in cerebellar parallel fibers and hippocampal Schaffer collaterals. It is most likely due to a well-controlled process that stops the fast repolarization at a membrane potential positive to resting membrane potential, leaving the membrane more excitable for ~100 ms during a slow, passive discharge of the membrane capacitance. The DAP helps reduce failures but can also cause uncontrolled bursting if it is not properly controlled. The voltage at which the fast repolarization stops, and the DAP starts, is close the activation range of both Na+ and Ca2+ voltage activated channels and is therefore essential for neuronal function.

Highlights

The after-potentials of the action potentials (“spikes”), either hyper- or de-polarizing relative to resting membrane potential, are excitability-controlling mechanisms. Such after-potentials have been extensively studied in regions near the soma where some of their functions are obvious: they reduce or increase the amount of current needed to reach threshold for spike initiation at the axon initial segment (AIS)
That may be one of the reasons considerably less is known about after-potentials in axons, in the very thin, typical cortical axons (TCAs)
The critical experiment to test if the hyperexcitability is specific to the activated axon is to measure the excitability when only one axon is activated. This was done on cerebellar parallel fibers with a somatic tight-seal electrode triggering a somatic spike and a separate electrode testing the threshold for spike activation of the axon (Palani et al, 2012)

Summary

Introduction

The after-potentials of the action potentials (“spikes”), either hyper- or de-polarizing relative to resting membrane potential, are excitability-controlling mechanisms. Such after-potentials have been extensively studied in regions near the soma where some of their functions are obvious: they reduce or increase the amount of current needed to reach threshold for spike initiation at the axon initial segment (AIS). When spikes in TCAs have been studied the focus has been mostly on the fast rather than the slow part of the spike This is because the shape of the fast spike has a well-established impact on transmitter release (Augustine, 1990; Sabatini and Regehr, 1997; Borst and Sakmann, 1999). The study of effects of after-potentials on transmitter release is relatively new (Clarke et al, 2016; Sierksma and Borst, 2017), and their influences on conduction properties like speed, endurance, bursting, and failures, which are the main topics of this article, have received even less attention

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