Human motoneuron firing behavior and single motor unit F-wave.

In motor control studies, the F-wave (a recurrent discharge evoked by an axonal antidromic volley) widely used for obtaining information on motoneuron pool behavior. However, such F-wave using is a matter of discussion and still has been not validated experimentally. The aim of the present study was investigation of F-wave properties of single firing motor units (MUs) in healthy humans, the properties, which could give evidence for F-wave origin in motoneuron soma and, therefore, could be used for estimation of a relation between MU firing and motoneuron firing behavior. In total, 91 MUs in five muscles of six healthy subjects, during gentle voluntary contractions, were studied. Peri-stimulus time histograms of single MUs were plotted. None of them revealed statistically significant increasing in MU firing probability at the F-wave latency. Analysis of relationships between characteristics of motoneuron firing behavior (mean firing frequency and target interspike interval duration) and properties of F-waves showed their independence. At the same time, it was found that F-waves were recorded in MUs, whose axons possessed the marked supernormal period in excitability recovery cycle after a discharge. Thus, the present results are in contrast to that which should be expected if the F-wave originated in the motoneuronal soma and could provide evidence for motoneuron firing behavior.

Evidence of two modes of spiking evoked in human firing motoneurones by Ia afferent electrical stimulation.

Neurone firing behaviour is a result of complex interaction between synaptic inputs and cellular intrinsic properties. Intriguing firing behaviour, delayed spiking, was shown in some neurones, in particular, in cat neocortical neurones and rat pyramidal hippocampal neurones. In contrast, the similar spiking mode was not reported for animal spinal motoneurones. In the present study, an attempt was made to look for possible evidence of delayed spiking in human motoneurones firing within the low-frequency, sub-primary range, characteristic for voluntary muscle contractions and postural tasks. Forty-seven firing motor units (MUs) were analyzed in ten experiments on three muscles (the flexor carpi ulnaris, the tibialis anterior, and the abductor pollicis brevis) in four healthy humans. Single MUs were activated by gentle voluntary muscle contractions. MU peri-stimulus time histograms, durations of inter-spike intervals, and motoneurone excitability changes within a target interspike interval were analyzed. It was found that during testing the firing motoneurone excitability by small, transient excitatory Ia afferent volley, depending firstly on volley timing within a target interspike interval and excitatory volley strength, the same motoneurone displayed either the direct short-latency response (the H-reflex) or the delayed response (with prolonged and variable latency). Thus, the findings, for the first time, provide evidence for a possibility of two modes of spiking in firing motoneurones. Methods of the estimation of delayed responses and their possible functional significance are discussed. It is emphasized that, for understanding of this issue, the integration of data from studies on experimental animals and humans is desirable.

Repetitive doublet firing in human motoneurons: evidence for interaction between common synaptic drive and plateau potential in natural motor control.

The firing behavior of spinal motoneurons (MNs) is a result of processing synaptic inputs by MN membrane properties, including plateau potentials, fundamentally explored in animals. However, there is much less data about a plateau potential role in human motor control. We explored human MN repetitive doublet firing during gentle isometric voluntary muscle contractions with the aim of revealing possible evidence for interaction between plateau potentials and common synaptic drive known as an important determinant of MN pool firing behavior. Single-motor unit (MU) repetitive firing of trapezius and triceps brachii was analyzed. Subjects were asked to recruit MUs capable of firing repetitive doublets. The analysis of interspike intervals (ISIs) of background firing of simultaneously recorded MUs showed that beyond doublet series ISIs varied, often in unison with significant correlation coefficients, demonstrating common synaptic drive. During doublet series, MUs showed persistent doublet ISIs (typically 4-7 ms) and a tendency to increase the number of doublets in series throughout the experiment. This was consistent with involvement of MN plateau potentials resulting in persistent delayed depolarization (underlying each doublet) and warm-up effect. Common synaptic drive "started" doublet series; probably both mechanisms controlled postdoublet ISIs. However, convincing effects of plateau potentials on MU firing behavior during single firing were not found. Thus our results suggest a plateau potential role in specifying the essential firing pattern, doubling, of some MUs rather than its effect on firing behavior of the MN pool, on the whole, during voluntary muscle contractions in humans. NEW & NOTEWORTHY Properties of human motoneuron repetitive doublet firing were explored during voluntary muscle contractions. It was shown for the first time that these properties seem to be consistent with properties of both plateau potentials, resulting in persistent delayed depolarization (underlying each doublet) and common synaptic drive, starting this unusual firing; both mechanisms could probably control postdoublet intervals. A convincing effect of plateau potentials on motoneuron single-spike firing, despite doublet firing, was not found.

Excitability and firing behavior of single slow motor axons transmitting natural repetitive firing of human motoneurons.

Excitability of motor axons is critically important for realizing their main function, i.e., transmitting motoneuron firing to muscle fibers. The present study was designed to explore excitability recovery and firing behavior in single slow axons transmitting human motoneuron firing during voluntary muscle contractions. The abductor digiti minimi, flexor carpi ulnaris, and tibialis anterior were investigated during threshold stimulation of corresponding motor nerves. Motor unit (MU) firing index in response to testing volleys evoking M-responses was used as a physiological measure of axonal excitability and its changes throughout a target interspike interval (ISI) were explored. It was shown that axons displayed an early irresponsive period (within the first ~2-5 ms of a target ISI) that was followed by a responsive period (for the next 5-17 ms of the ISI), in which MUs fired axonal doublets, and a later irresponsive period. At the beginning of the responsive period, M-responses showed small latency delays. However, since at that ISI moment, MUs displayed excitability recovery with high firing index, slight latency changes may be considered as a functionally insignificant phenomenon. The duration of axonal doublet ISIs did not depend on motoneuron firing frequencies (range 4.3-14.6 imp/s). The question of whether or not traditionally described axonal recovery excitability cycle is realistic in natural motor control is discussed. In conclusion, the present approach, exploring, for the first time, excitability recovery in single slow axons during motoneuron natural activation, can provide further insight into axonal firing behavior in normal states and diseases.NEW & NOTEWORTHY Excitability of single slow axons was estimated by motor unit firing index in response to motor nerve stimulation, and its changes throughout a target interspike interval were explored during transmitting human motoneuron natural firing. It was found that axons exhibited early irresponsive, responsive, and later irresponsive periods. Findings question whether the traditionally described axonal excitability recovery cycle is realistic in natural motor control.

F-wave of single firing motor units: correct or misleading criterion of motoneuron excitability in humans?

Motoneuron excitability is a critical property for information processing during motor control. F-wave (a motoneuronal recurrent discharge evoked by a motor antidromic volley) is often used as a criterion of motoneuron pool excitability in normal and neuromuscular diseases. However, such using of F-wave calls in question. The present study was designed to explore excitability of single low-threshold motoneurons during their natural firing in healthy humans and to ascertain whether F-wave is a correct measure of motoneuronal excitability. Single motor units (MUs) were activated by gentle voluntary muscle contractions. MU peri-stimulus time histograms and motoneuron excitability changes within a target interspike interval were analysed during testing by motor antidromic and Ia-afferent volleys. It was found that F-waves could be occasionally recorded in some low-threshold MUs. However, during evoking F-wave, in contrast with the H-reflex, peri-stimulus time histograms revealed no statistically significant increase in MU discharge probability. Moreover, surprisingly, motoneurons appeared commonly incapable to fire a recurrent discharge within the most excitable part of a target interval. Thus, the F-wave, unlike the H-reflex, is the incorrect criterion of motoneuron excitability resulting in misleading conclusions. However, it does not exclude the validity of the F-wave as a clinical tool for other aims. It was concluded that the F-wave was first explored in low-threshold MUs during their natural firing. The findings may be useful at interpretations of changes in the motoneuron pool excitability in neuromuscular diseases.

Triplet firing origin in human motor units: emerging hypotheses.

A specific feature of motor unit (MU) firing behaviour is rhythmic trains of single discharges at low rate resulting from the prolonged motoneuronal afterhyperpolarization. However, some MUs exhibit occasional doublets with uniquely short interspike intervals (2.5-20.0 ms). Motoneuronal delayed depolarization is commonly accepted to be doublet underlying mechanism. Apart from doublets, much scarcer MU triple discharges were described, but their mechanisms are disputable. The aim of the present study was to analyse MU triplet firing origin in healthy humans. MU triple discharges occasionally arising during gentle voluntary muscle contractions were compared with those arising in axons during motor nerve stimulation. Firing pattern was analysed in 109 MUs of four muscles: the tibialis anterior, the flexor carpi ulnaris, the abductor pollicis brevis, and the abductor digiti minimi. Our findings present evidence that during voluntary contractions two kinds of MU triplet firing can be occasionally observed: "true" motoneuronal triplets (interspike intervals of 3.6-17.3 ms) with the delayed depolarization as the possible underlying mechanism and axonal triple discharges including the M-response and F-wave. The findings can be useful not only for understanding mechanisms of the very rare motoneuronal firing in healthy humans but also for estimation of pathological triplet firing origin.

Motor unit firing pattern: evidence for motoneuronal or axonal discharge origin?

In neuromuscular diseases, a fasciculation origin is disputed. In some reports, it was suggested that motor unit firing pattern alone is evidence for motoneuronal or axonal fasciculations; namely interspike intervals of approximately 5 ms (doublet intervals) provide evidence for the axonal firing. To clarify the reliability of the suggestion, we compared doublet intervals originated in motoneurons and their axons in healthy humans. For this aim, the H-reflex and M-response of single motor units were elicited during gentle voluntary muscle contractions. Peri-stimulus time histograms allowed reliable judgment about a doublet origin: motoneuronal (at the H-reflex latency) or axonal (at the M-response latency). Significant difference between motoneuronal and axonal doublet intervals was absent. It was concluded that doublet interval alone cannot be the reliable criterion for an axonal firing origin; additional evidences are needed for this conclusion, for example, the appearance of the F-wave. The approach may be used as an additional estimation of mechanisms underlying motor unit diseases.

Repetitive doublet firing of motor units: evidence for plateau potentials in human motoneurones?

During voluntary muscle contraction, human motoneurones can exhibit specific discharge patterns: single and repetitive doublets. Delayed depolarization has been accepted as the mechanism underlying single doublets. Repetitive doublet firing has been studied much less and its controlling mechanisms remain obscure. The aim of the present study was to examine properties of repetitive doublets in human motoneurones and to consider their underlying potential mechanisms. It was found that 22 of 41 (53.7%) lower-threshold motor units (MUs) in the trapezius and 15 of 42 (35.7%) MUs in triceps brachii displayed repetitive doublets with the mean interspike intervals (ISIs) of 5.5 +/- 1.1 and 6.4 +/- 2.6 ms, respectively. Each doublet was followed by a prolonged post-doublet ISI. The analysis of properties of repetitive doublets showed that they were typically initiated in quiescent motoneurones rather than in firing ones (appearing just at recruitment in an all-or-none manner) and could only be maintained at a certain level of muscle contraction. Repetitive doublets were interrupted either voluntarily (by the subject), or spontaneously with sudden transition from doublet firing to single discharges-the firing behaviour that may be referred to as a firing-pattern "jump". The properties of doublet firing seem to be consistent with traits of motoneurone firing in the presence of plateau potentials reported in animal studies. It was suggested that the potential mechanisms underlying repetitive doublet firing could include a delayed depolarization as the primary determinant, which likely could become persistent probably due to a plateau potential activated in parallel with a common synaptic input.