Neuromodulatory Contribution to Muscle Force Production after Short-Term Unloading and Active Recovery

Purpose: Prior evidence has shown that neural factors contribute to the loss of muscle force after skeletal-muscle disuse. However, little is known about the specific neural mechanisms altered by disuse. Persistent inward current (PIC) is an intrinsic property of motoneurons responsible for prolonging and amplifying the synaptic input, proportionally to the level of neuromodulation, thus influencing motoneuron discharge rate and force production. Here, we hypothesized that short-term unilateral lower-limb suspension (ULLS) would reduce the neuromodulatory input associated with PICs, contributing to the reduction of force generation capacity. Additionally, we tested whether physical exercise would restore the force generation capacity by re-establishing the initial level of neuromodulatory input. Methods: In 12 young adults, we assessed maximal voluntary contraction (MVC) pre- and post- 10 days of ULLS and following 21 days of active recovery (AR) based on resistance exercise. PIC was estimated from high-density surface electromyograms of the vastus lateralis muscle as the delta frequency (∆F) of paired motor units calculated during isometric ramped contractions. Results: The values of ∆F were reduced after 10 days of ULLS (-33%, p < 0.001), but were fully re-established after the AR (+29.4%, p < 0.001). The changes in estimated PIC values were correlated (r = 0.63, p = 0.004) with the reduction in MVC after ULLS (-29%, p = 0.002) and its recovery after the AR (+28.5%, p = 0.003). Conclusions: Our findings suggest that PIC estimates are reduced by muscle disuse and may contribute to the loss of force production and its recovery with exercise. Overall, this is the first study demonstrating that, in addition to peripheral neuromuscular changes, central neuromodulation is a major contributor to the loss of force generation capacity after disuse, and can be recovered after resistance exercise.