Maturation of persistent and hyperpolarization-activated inward currents shapes the differential activation of motoneuron subtypes during postnatal development.

Simon A Sharples,Gareth B Miles

doi:10.7554/elife.71385

Abstract

The size principle underlies the orderly recruitment of motor units; however, motoneuron size is a poor predictor of recruitment amongst functionally defined motoneuron subtypes. Whilst intrinsic properties are key regulators of motoneuron recruitment, the underlying currents involved are not well defined. Whole-cell patch-clamp electrophysiology was deployed to study intrinsic properties, and the underlying currents, that contribute to the differential activation of delayed and immediate firing motoneuron subtypes. Motoneurons were studied during the first three postnatal weeks in mice to identify key properties that contribute to rheobase and may be important to establish orderly recruitment. We find that delayed and immediate firing motoneurons are functionally homogeneous during the first postnatal week and are activated based on size, irrespective of subtype. The rheobase of motoneuron subtypes becomes staggered during the second postnatal week, which coincides with the differential maturation of passive and active properties, particularly persistent inward currents. Rheobase of delayed firing motoneurons increases further in the third postnatal week due to the development of a prominent resting hyperpolarization-activated inward current. Our results suggest that motoneuron recruitment is multifactorial, with recruitment order established during postnatal development through the differential maturation of passive properties and sequential integration of persistent and hyperpolarization-activated inward currents.

Highlights

Fine control of muscle force is a prerequisite for the generation of complex movement
We set out to address whether motoneuron recruitment, which we assayed based on the current required to elicit repetitive firing, is purely dependent on passive properties, as would be predicted by the size principle, or whether functional classes of spinal motoneurons possess distinct electrophysiological properties that help ensure orderly recruitment of motoneuron subtypes
We used postnatal development of the mouse as a model to dissect the relative importance of motoneuron intrinsic properties to the establishment of orderly recruitment during the emergence of fine motor control

Summary

Introduction

Fine control of muscle force is a prerequisite for the generation of complex movement. Variations in the complement of ion channels expressed by subtypes of spinal motoneurons have been demonstrated and their roles in producing non-linear firing behaviours described (Bos et al, 2018; Brocard, 2019; Heckman et al, 2008b; Soulard et al, 2020) Many of these currents are activated below the spike threshold, meaning their differential expression is likely to contribute to orderly recruitment across motoneuron subtypes (Zhang and Dai, 2020). To address the role of specific ion channels in motoneuron subtype recruitment, we studied differences in the intrinsic properties and underlying currents that contribute to the activation of putative fast and slow motoneurons, which were identified based on delayed and immediate firing profiles during whole cell patch clamp electrophysiological recordings in lumbar spinal cord slices of postnatal mice Whilst recruitment is influenced by size, activation properties of inward currents, which are differentially expressed in motoneuron subtypes, ensure orderly recruitment of functionally defined subtypes of spinal motoneurons

Results

Discussion

Methods