Human motor unit discharge patterns reveal differences in neuromodulatory and inhibitory drive to motoneurons across contraction levels

Abstract

All motor commands converge onto motor units (MUs), which transduce the signals into mechanical actions of muscle fibers. This process is highly nonlinear because of combinations of ionotropic (excitatory/inhibitory) and metabotropic (neuromodulatory) inputs. Neuromodulatory inputs facilitate dendritic persistent inward currents, which introduce nonlinearities in MU discharge patterns and provide insights into the structure of motor commands. Here, we investigated the relative contribution of neuromodulation and the pattern of inhibition to modulate human MU discharge patterns with contraction forces up to 70% maximum. Leveraging MU discharge patterns identified from three human muscles [tibialis anterior (TA) and vastus lateralis and medialis], we show that with increased contraction force the onset-offset discharge rate hysteresis (DF) increased while ascending MU discharge patterns become more linear, with lower slopes. In a follow-up experiment, we demonstrated that the observations of increased DF and more linear ascending MU discharge patterns with greater contraction force are maintained even when accounting for contraction duration and rate of force increase. We then reverse-engineered TA MU discharge patterns, using highly realistic in silico motoneuron pools to substantiate the inferred physiological mechanisms from human recordings. We demonstrate a sharply restricted solution space, whereby the contraction force-induced changes in experimentally obtained MU discharge patterns can only be recreated with increased neuromodulation and a more reciprocal (i.e. push-pull) inhibitory pattern. In summary, our experimental and computational data suggest that neuromodulation and inhibitory patterns are uniquely shaped to generate discharge patterns that support force increases across a large proportion of the motor pool’s recruitment range. NEW & NOTEWORTHY How the structure of motor commands is modified to scale motor output is largely speculative despite its critical role in the neural control of movement. Here, we demonstrate that human motor unit discharge patterns become more linear and exhibit greater discharge rate hysteresis with greater contraction force. These experimentally observed patterns can only be replicated in silico with biophysical spinal motoneuron models by increasing neuromodulation and a shift from tonic to push-pull excitation-inhibition synaptic control.