Comparison of injury and development in the neuromuscular system

Comparisons of development and regeneration have suggested that axotomized motoneurons and denervated muscles undergo dedifferentiation to an embryonic state with recovery of adult properties after reinnervation. Using electrophysiological and radioligand-binding techniques to monitor axonal size and numbers of extrajunctional acetylcholine receptors in axotomized motoneurons and denervated muscles respectively, we have demonstrated that this dedifferentiation is limited. We suggest that this limited dedifferentiation may be adaptive for survival, regeneration and reinnervation. Correlative physiological and histochemical studies of reinnervated motor units in cat and rat hindlimb muscles show that the processes of regeneration and reinnervation differ in a number of fundamental ways from developmental processes of axonal growth and muscle innervation. Enlargement of motor units after partial nerve injuries does not appear to be limited to the size of the neonatal motor unit as originally suggested but may be influenced by factors operating at the level of axonal branching. Regeneration after complete and partial nerve injuries is a random process in contrast to the specific nature of the innervation of targets during development. Regenerating axons frequently fail to make connections with their original muscles and newly reinnervated motor units contain muscle fibres which formerly belonged to several different motor units. Despite this misdirection of regenerating nerve fibres, neuromuscular plasticity restores neuromuscular properties to the extent that these are appropriate at the single motor unit level for the gradation of force by the orderly recruitment of units during movement.