Simon A. Sharples, PhD 🇨🇦 (@neurosharps.bsky.social)

I love a good story about persistent inward currents (PICs). But I’ve always wondered: could other ion channels contribute to the motoneuron firing behaviours we usually attribute to PICs? Our new preprint suggests the answer might be yes. www.biorxiv.org/content/10.6...

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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 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. ### Competing Interest Statement The authors have declared no competing interest. Royal Society, NIF\R1\180091 Canadian Institute for Health Research, PDF - 202012MFE - 459188 - 297534 https://www.biorxiv.org/content/10.64898/2026.03.12.711366v1