Developmental mechanisms contributing to non-linear firing dynamics in spinal motoneurons of the postnatal mouse

The intrinsic properties of spinal motoneurons support flexible movement, including the maintenance of postural tone. Motoneurons can produce sustained action potential output that outlasts synaptic input, a phenomenon traditionally attributed to persistent inward currents (PICs) mediated by sodium and calcium channels. Using whole-cell patch-clamp electrophysiology, we examined how specific ion channels contribute to PIC maturation and non-linear firing dynamics that allow motoneurons to sustain their output in fast and slow lumbar motoneurons across postnatal development in mice. PIC amplitude and non-linear firing dynamics increased after weight-bearing in fast but not slow motoneurons. Blocking Na_V1.6 channels reduced PIC amplitude at both pre- and post-weight-bearing stages, whereas L-type calcium channel blockade only reduced PICs after weight-bearing emerged. However, reducing PIC amplitude by blocking these channels, either individually or in parallel, did not abolish sustained firing hysteresis, which may be because PICs are not yet fully established at this stage of postnatal development. Unexpectedly, activation of muscarinic receptors increased PIC amplitude while promoting adaptive firing dynamics, suggesting that PICs alone do not account for sustained firing hysteresis. We also found that pharmacological manipulation of potassium currents mediated by KCNQ and K_V1.2 channels produced substantial changes in firing dynamics. Strikingly, blocking hyperpolarization-activated cyclic nucleotide-gated channels promoted sustained firing dynamics and led to the emergence of self-sustained firing in fast motoneurons. These results indicate that PICs and non-linear firing dynamics mature together and extend the current framework on non-linear firing dynamics of motoneurons to include additional voltage-gated ion channels. KEY POINTS: Persistent inward currents (PICs) and recruitment-derecruitment hysteresis increase in parallel in fast, but not slow, motoneurons following the onset of hindlimb weight-bearing. Increased expression or function of L-type calcium channels may contribute to enhanced PIC amplitude in fast motoneurons after weight-bearing emerges. Blocking Na_V1.6 or L-type calcium channels did not reduce sustained firing hysteresis in fast motoneurons. KCNQ channels oppose PICs and, together with K_V1.2 channels, shape recruitment-derecruitment asymmetry, thereby modulating firing hysteresis in fast motoneurons. Hyperpolarization-activated cyclic nucleotide-gated channels generate a resting H-current that delays recruitment, modulates firing hysteresis, and prevents the emergence of self-sustained firing in fast motoneurons.