Role of motoneurons in the generation of muscle spasms after spinal cord injury

Abstract

Motoneurons in the spinal cord have intrinsic voltage-dependent persistent inward currents (PICs; e.g. persistent calcium currents) that amplify synaptic inputs by three- to five-fold in addition to providing a sustained excitatory drive that allows motoneurons to fire repetitively following a brief synaptic excitation. In this study, we examined whether prolonged involuntary muscle spasms in subjects with long-term injury to the spinal cord are mediated by the activation of PICs in the motoneuron. To examine this in the human, we used a paired motor unit analysis technique where the firing frequency of one motor unit of the pair (control unit) was used to estimate the synaptic drive to the motoneuron pool, including the drive to a second higher-threshold motor unit of the pair (test unit). The degree to which a motoneuron PIC helped to sustain the discharge of a test motor unit (self-sustained firing) was determined from the reduction in control unit firing at de-recruitment (DeltaF) compared with recruitment of the test unit. This DeltaF value corresponds to the reduction in synaptic drive needed to counteract the intrinsic PIC and, thus, was used an indirect measure of this current. In the nine motor unit pairs studied, the average estimated synaptic drive, or control unit firing rate, required to recruit a test motor unit at the onset of a muscle spasm was significantly higher (by 43%) than the estimated synaptic drive during de-recruitment at the end of a muscle spasm. This indicated that a motoneuron PIC, and associated self-sustained firing, facilitated the firing of the test units during the prolonged muscle spasms. In addition, in all subjects tested (seven out of seven), we observed that following a muscle spasm or voluntary contraction, spontaneous and self-sustained firing of motor units could continue for many seconds, even minutes, at very low discharge rates (average 5.2 +/- 1.6 Hz) with extremely low spike-to-spike variability (coefficient of variation = 5.4 +/- 1.6%). Moreover, increases in synaptic drive (noise) to the spontaneously firing units with voluntary muscle contractions or muscle spasms increased both the mean firing rate of the motor units in addition to their firing variability. This suggests that the slow spontaneous firing commonly observed in chronic spinal injury likely occurs without appreciable synaptic noise and is likely driven to a substantial degree by PICs intrinsic to the motoneuron because it is self-sustained and very regular.