Persistent inward currents in spinal motoneurones: how can we study them in human participants?

Activation of a motoneurone occurs when excitatory synaptic input from descending motor pathways, or sensory projections, is sufficient to bring the membrane potential of the motoneurone above its firing threshold. The input–output gain of motoneurones is enhanced by monoamine neuromodulators released from raphe-spinal neurons (serotonin, 5-HT) and locus coeruleus neurons (noradrenaline, NA). These pathways form monosynaptic connections with the dendrites of motoneurones and have multiple effects on motoneurone excitability. Notably, 5-HT and NA have strong facilitation effects on voltage-gated persistent inward currents (PICs), which amplify synaptic input and promote the self-sustained discharge of motoneurones. In animal preparations with restricted neuromodulator release, intracellular recordings of motoneurones reveal that increasing the magnitude of injected current increases discharge rate linearly. However, in the presence of neuromodulation and PIC activation, the relationship between injected current and discharge rate becomes non-linear. This is reflected in the hysteresis between the magnitude of injected current needed for recruitment and at de-recruitment, one of many PIC-induced non-linearities (e.g. acceleration of firing, firing rate saturation). Compared to recruitment, injected current is lower at de-recruitment as less excitatory input is needed to maintain ongoing motoneurone discharge as PICs are active and are generating a strong intrinsic depolarization.