The role of computer simulations in the investigation of mechanisms underlying rhythmic firing of human motoneuron

Abstract

Over the past few decades, a great deal of information on the function of mammalian motor neurons (MNs) has been obtained from intracellular recordings collected in acute animal experiments. Nowadays, it is becoming increasingly clear that human experiments in which MNs are tested under physiological conditions are equally important for further MN research.Investigation of human MNs is possible by recording the potentials of single motor units (MUs), which respond to action potentials from their MNs in the one-to-one fashion. Thus the analysis of MU firing patterns, based on basic knowledge of the MN physiology obtained from animal experiments and verified by computer simulations, allows the evaluation of the biophysical properties of human MNs.The MN models can be roughly classified as threshold-crossing and compartmental. Threshold-crossing models allowed verification of the methods for assessing the shape of synaptic volleys by analyzing the stimulus-correlated MN discharge patterns. They also helped in the development of methods for estimation of afterhyperpolarization of human MNs.The earliest compartmental models did not take into account the effects of persistent inward currents (PICs), which are now considered to be one of the most important factors in shaping human MN discharge patterns. Recent MN models increasingly focus on PICs and their interaction with synaptic inputs. It has been shown that different combinations of the two can produce various MU discharge patterns, including those mimicking the lack of effect of neuromodulators.This review shows how computer simulations support scientists in obtaining information from human experiments.