CONTRIBUTIONS OF PATHWAY AND NEURON TO PREFERENTIAL MOTOR REINNERVATION

Motor axons regenerating after transection of mixed nerve preferential ly reinnervate distal muscle branches, a process termed preferential m otor reinnervation (PMR). Motor axon collaterals appear to enter both cutaneous and muscle Schwann cell tubes on a random basis. Double-labe ling studies suggest that PMR is generated by pruning collaterals from cutaneous pathways while maintaining those in motor pathways (the ''p runing hypothesis''). If all collaterals projecting to muscle are save d, then stimulation of regenerative sprouting should increase specific ity by increasing the number of motoneurons with at least one collater al in a muscle pathway, in the current experiments, collateral sprouti ng is stimulated by crushing the nerve proximal to the repair site bef ore suture, a maneuver that also conditions the neuron and predegenera tes the distal pathway. Control experiments are performed to separate these effects from those of collateral generation. Experiments were pe rformed on the rat femoral nerve and evaluated by exposing its termina l cutaneous and muscle branches to HRP or Fluoro-Gold. Crush proximal to the repair site increased motor axon collaterals at least fivefold and significantly increased the percentage of correctly projecting mot oneurons, consistent with the pruning hypothesis. Conditioning the ner ve with distal crushes before repair had no effect on specificity. A g raft model was used to separate the effects of collateral generation a nd distal stump predegeneration. Previous crush of the proximal femora l nerve significantly increased the specificity of fresh graft reinner vation. Stimulation of regenerative collateral sprouting thus increase d PMR, confirming the pruning hypothesis. However, this effect was ove rshadowed by the dramatic specificity with which predegenerated grafts were reinnervated by fresh uncrushed proximal axons. These unexpected effects of predegeneration on specificity could involve a variety of possible mechanisms and warrant further study because of their mechani stic and clinical implications.