Motor neurons can preferentially reinnervate cutaneous pathways

Previous work in the rat femoral nerve has shown that regenerating motor neurons preferentially reinnervate a terminal nerve branch to muscle as opposed to skin. This process has been termed preferential motor reinnervation (PMR) and has been interpreted as evidence that regenerating motor axons can differentiate between Schwann cell tubes that reside in muscle versus cutaneous terminal pathways. However, much of this previous work has been confounded by motor axons having access to target muscle during the regeneration period. The present experiments prevented muscle contact by regenerating motor axons. By 8 weeks under these conditions, significantly more motor neurons reinnervated the cutaneous pathway rather than the original muscle pathway. We propose that cutaneous and muscle terminal pathways are not inherently different in terms of their ability to support regeneration of motor neurons. Rather, we suggest that it is the relative level of trophic support provided by each nerve branch that determines whether motor axons will remain in that particular branch. Within the context of the femoral nerve model, our results suggest a hierarchy of trophic support for regenerating motor axons with muscle contact being the highest, followed by the length of the terminal nerve branch and/or contact with skin.