Motor unit alterations with muscle disuse: what's new?

Skeletal muscle is a highly plastic tissue that quickly adapts to changes in mechanical load. Conditions inducing a reduction in muscle loading, commonly experienced across the lifespan after musculoskeletal injury, disease and surgery, determine a marked decrease in muscle mass and force. Interestingly, the reported loss of muscle function largely exceeds that of muscle size, suggesting an impairment in the intrinsic capacity of muscle force production (Monti et al., 2021). Considering the relevance of these aspects for translational medicine, unravelling the mechanisms underpinning these disuse-induced maladaptations has been a central challenge of modern integrative physiology for decades. Several unloading-mimicking experimental models have been developed, including bed rest, unilateral lower limb suspension (ULLS) and unilateral lower limb immobilisation (ULLI) (Fig. 1). During bed rest, participants are asked to lie without the possibility of standing up or leaving the bed (Monti et al., 2021). Differently, during ULLS one leg is suspended and kept slightly flexed using straps (Sarto et al., 2022), while during ULLI a brace is employed to abolish the movement of one limb (Inns et al., 2022). The application of these unloading models in research studies provided essential advances in our understanding of how disuse can impact muscle integrity. However, some relevant physiological aspects remain poorly investigated. In particular, despite disuse having been previously defined as ‘reduction of load and number of action potentials delivered by motoneurons’ (Reggiani, 2015), information regarding adaptations of motor unit (MU) properties in response to unloading is surprisingly scant. Indeed, only a few pioneering studies have investigated this aspect, reporting an altered firing rate modulation of individual MUs in the adductor pollicis and first dorsal interosseous following 6–8 weeks of cast immobilization of the hand (e.g. Duchateau & Hainaut, 1990). A deeper knowledge of muscle electrophysiological alterations following disuse and their underlying mechanisms represent a fundamental step for the development of effective countermeasures. In a recent issue of The Journal of Physiology, Inns et al. (2022) provide novel data on MU alterations with ULLI in the human vastus lateralis, a large muscle of the quadriceps. Vastus lateralis is important for mobility and the performance of daily life motor tasks (e.g. standing from a chair, climbing stairs) and this increases the clinical relevance of the investigation. Ten young healthy participants volunteered in this study; data collection was performed at baseline and after 15 days of knee brace-induced immobilization. The authors performed a broad evaluation of muscle performance, including an assessment of knee extensor isometric maximum voluntary contraction (MVC), muscle power and force control (force steadiness). Panoramic ultrasound performed at 50% of femur length was employed to assess changes in muscle cross-sectional area (CSA). Finally, to evaluate MU characteristics, a state-of-the-art intramuscular electromyographic (iEMG) evaluation was carried out by inserting a needle electrode at the vastus lateralis