Persistent inward currents in human motoneurons: Emerging evidence and future directions

The manner in which motoneurons respond to excitatory and inhibitory inputs depends strongly on how their intrinsic properties are influenced by the neuromodulators serotonin and noradrenaline. These neuromodulators enhance the activation of voltage‑gated channels that generate persistent (long-lasting) inward sodium and calcium currents (PICs) into the motoneurons. PICs are crucial for initiating, accelerating, and maintaining motoneuron firing. A greater accessibility to state-of-the-art techniques that allows both the estimation and examination of PIC modulation in tens of motoneurons in vivo has rapidly evolved our knowledge of how motoneurons amplify and prolong the effects of synaptic input. We are now in a position to gain substantial mechanistic insight into the role of PICs in motor control at an unprecedented pace. The present review briefly describes the effects of PICs on motoneuron firing and the methods available for estimating them before presenting the emerging evidence of how PICs can be modulated in health and disease. Our rapidly developing knowledge of the potent effects of PICs on motoneuron firing has the potential to improve our understanding of how we move, and points to new approaches to improve motor control. Finally, gaps in our understanding are highlighted and methodological advancements suggested to encourage readers to explore outstanding questions to further elucidate PIC physiology.