The neuromuscular junction: a critical component of functional recovery after peripheral nerve injury

Peripheral nerve injury can result in potentially devastating neurological deficits and often disproportionately impacts young workers. Recovery of motor function after peripheral nerve injury requires the regeneration of the nerve from the site of injury to the neuromuscular junction (NMJ), where signals must be transduced effectively across the synapse, resulting in target muscle contraction. For reasons that are not fully understood, after about 18 months of denervation, functional NMJs fail to recapitulate. This, in combination with the slow velocity of axon regeneration, significantly limits both the window of opportunity for intervention and surgical reconstruction options. Here, we review what is currently known with respect to NMJ physiology, anatomy, development, and changes after injury. We also highlight knowledge gaps and opportunities for study with the goal of developing novel, NMJ-focused avenues of treatment for patients after peripheral nerve injury.