Excitability properties of single human motor axons: are all axons identical?

INTRODUCTION Under natural motor control, repetitive firing of motoneurons is transmitted by their motor axons to muscle fibers in the “one to one” fashion that allows the analysis of human motoneuron firing via recordings of motor unit (MU) action potentials (see Kernell, 2006; Heckman and Enoka, 2012). However, when axons are diseased or damaged, local increasing axonal excitability may result in disturbing this basic principle and creating an additional focus of excitation in an axon itself, leading to different symptoms, including MU spontaneous discharges. In order to gain an insight into possible pathophysiological mechanisms underlying changes in axonal excitability, many studies were addressed exploring axonal excitability properties in healthy humans and their fundamental characteristics have been obtained (reviewed by Bostock et al., 1998; Burke et al., 2001; Nodera and Kaji, 2006). In particular, axonal activation has been found to be followed by certain excitability recovery cycle as tested commonly after a supramaximal conditioning stimulus (e.g., Kiernan et al., 1996; Bostock et al., 1998; Murray and Jankelowitz, 2011) or after the cessation of maximal voluntary muscle contractions (Vagg et al., 1998; Kuwabara et al., 2001; Rossi et al., 2012). Traditionally, axon excitability properties were explored for whole motoneuronal pool, using a compound muscle action potential (CMAP), without analysing the behavior of single MUs. However, such approach gives no information on the excitability properties of motor axons belonging to different types of MUs. A few reports, beginning with the seminal studies of Bergmans (1970, 1973), addressed the excitability properties of single motor axons, as a rule, low-threshold to electrical stimulation and thus belonging to large MUs, high-threshold to voluntary muscle contraction (Borg, 1980; Bostock and Baker, 1988; Shefner et al., 1996; Hales et al., 2004; Bostock et al., 2005). At the same time there are no data on the excitability properties of axons belonging to small, slow MUs during their natural activation, while these MUs are essential part of motoneuronal pools as they are primarily activated during both voluntary movements and the maintenance of posture, as well as at reflex activation. The question arises of whether or not the excitability properties of these axons are similar to that of MUs with high-threshold to voluntary muscle contraction. Our findings reported below give some possibility to start the discussion of this question.