C-bouton components on rat extensor digitorum longus motoneurons are resistant to chronic functional overload.

Roger W P Kissane,Stuart Egginton,Robert M Brownstone,Peter G Tickle,Calvin C Smith,Arash Ghaffari‐Rafi,Samit Chakrabarty

doi:10.1111/joa.13439

Abstract

Mammalian motor systems adapt to the demands of their environment. For example, muscle fibre types change in response to increased load or endurance demands. However, for adaptations to be effective, motoneurons must adapt such that their properties match those of the innervated muscle fibres. We used a rat model of chronic functional overload to assess adaptations to both motoneuron size and a key modulatory synapse responsible for amplification of motor output, C‐boutons. Overload of extensor digitorum longus (EDL) muscles was induced by removal of their synergists, tibialis anterior muscles. Following 21 days survival, EDL muscles showed an increase in fatigue resistance and a decrease in force output, indicating a shift to a slower phenotype. These changes were reflected by a decrease in motoneuron size. However, C‐bouton complexes remained largely unaffected by overload. The C‐boutons themselves, quantified by expression of vesicular acetylcholine transporter, were similar in size and density in the control and overload conditions. Expression of the post‐synaptic voltage‐gated potassium channel (KV2.1) was also unchanged. Small conductance calcium‐activated potassium channels (SK3) were expressed in most EDL motoneurons, despite this being an almost exclusively fast motor pool. Overload induced a decrease in the proportion of SK3+ cells, however, there was no change in density or size of clusters. We propose that reductions in motoneuron size may promote early recruitment of EDL motoneurons, but that C‐bouton plasticity is not necessary to increase the force output required in response to muscle overload.

Highlights

Evolution of the mammalian motor system affords many morphologically and functionally different animals to thrive in diverse environmental conditions (Brownstone, 2020)
The results presented here demonstrate that chronic overload of the rat extensor digitorum longus (EDL) muscle induces significant adadptations to muscle fibre capiliary innervation and contractile properties
21 days functional overload resulted in an increase in EDL capiliary-to-fibre ratio and fatigue resistance, paralleled by a decrease in twitch and tetanic force production

Summary

| INTRODUCTION

Evolution of the mammalian motor system affords many morphologically and functionally different animals to thrive in diverse environmental conditions (Brownstone, 2020). Assessments of motoneuron properties at a chronic stage showed a shift towards those of the reinnervated muscle, suggesting mechanisms of plasticity exist within the motor unit to match muscle and motoneuron properties Physiological stimuli such as exercise induce functional adaptations in motoneuron properties: endurance training in rats induces increases in the motoneuron medium after hyperpolarisation (mAHP) amplitude, consistent with a shift to a more fatigue-resistant phenotype (Gardiner et al, 2006). Our results show that in conjunction with a slower muscle phenotype following overload, there is a corresponding decrease in motoneuron size We suggest that this central adaptation may compensate for increased functional demands by reducing motoneuron rheobase and increasing excitability. Anatomical plasticity of the neuromodulatory C-bouton complex is not necessary to produce increased force output in this model of chronic functional overload

| Ethical approval

2.11 | Data Availability Statement

| RESULTS

Findings

| DISCUSSION