Peripheral pathways regulate motoneuron collateral dynamics.

Motor axons regenerating after repair of mixed nerve reinnervate pathways leading to muscle more often than those leading to skin [preferential motor reinnervation (PMR)]. Motoneurons that initially project collaterals to both muscle and skin prune incorrect projections to generate specificity. The number of motor axon collaterals maintained entirely within cutaneous or muscle pathways, however, is unknown. To overcome this shortcoming, dorsal root ganglion excision has been used to allow only motor axons to regenerate after a peripheral lesion. Motor axon number in reinnervated cutaneous and muscle pathways can then be correlated with the number of parent motoneurons determined by retrograde labeling. The number of collaterals per neuron can be calculated for each environment and the relative roles of pathway and end organ assessed by blocking the distal pathways to prevent target reinnervation. Without sensory competition, PMR develops in two stages: a limited response to muscle nerve and then a robust response to muscle that may involve retrograde signaling to the proximal pathway. Motoneurons maintain more collaterals in cutaneous nerve than in muscle nerve, even without muscle contact. This difference could result either from increased collateral formation in cutaneous nerve or from increased collateral pruning in muscle nerve. In either instance, these findings confirm that muscle and cutaneous pathways have functionally significant identities that can be recognized by motor axons and can regulate their arborization. Decreased arborization in muscle pathways could promote regeneration by focusing neuronal resources on high-yield projections; increased arborization in cutaneous pathways, conversely, would enhance pathfinding abilities.