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

Abstract

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 Nav1.6 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--either individually or in combination--did not abolish sustained firing hysteresis. Unexpectedly, activation of muscarinic receptors increased PIC amplitude while promoting adaptive firing dynamics, suggesting that PICs alone do not drive this behavior. Instead, pharmacological manipulation of potassium currents mediated by KCNQ and Kv1.2 channels, which oppose PICs, produced substantial changes in firing dynamics. Strikingly, blocking HCN channels promoted sustained firing dynamics and led to the emergence of self-sustained firing in fast motoneurons. These results indicate that while PICs and non-linear firing dynamics mature together, sustained firing relies on mechanisms beyond PICs, with potassium and HCN channels playing key modulatory roles. Key PointsO_LIPersistent inward currents (PICs) and recruitment-derecruitment hysteresis increase in parallel in fast, but not slow, motoneurons following the onset of hindlimb weight bearing. C_LIO_LIIncreased expression or function of L-type calcium channels may contribute to enhanced PICs in fast motoneurons after weight bearing emerges. C_LIO_LINeither Nav1.6 nor L-type calcium channels are required for sustained firing hysteresis in fast motoneurons. C_LIO_LIKCNQ channels attenuate PICs and, together with Kv1.2 channels, shape recruitment-derecruitment asymmetry, thereby modulating firing hysteresis in fast motoneurons. C_LIO_LIHCN channels generate a resting H-current that delays recruitment, modulates firing hysteresis, and prevents the emergence of self-sustained firing in fast motoneurons. C_LI