Motor neuron regeneration accuracy: balancing trophic influences between pathways and end-organs

The key to recovery of function following peripheral nerve lesions is guiding axons back to their original target end-organs. The parent femoral nerve splits into two comparable terminal pathways: one to the muscle and the other to the skin. Normally, motor neurons only innervate the pathway to the muscle, but after the parent nerve is repaired regenerating motor neurons are often misrouted to the skin. When the muscle and skin pathways remain connected to their respective targets after the parent nerve is repaired, reinnervation favors the muscle pathway. If contact with the muscle is instead prevented, reinnervation favors the pathway to the skin. Here we examine whether shortening the skin pathway can alter motor reinnervation accuracy when the muscle pathway remains connected to the muscle. We demonstrate that reducing the influence of the skin pathway results in a more rapid and extensive reinnervation of the muscle pathway. These findings suggest that the relative balance of trophic influences from the pathways and their end-organs is an important determinant of motor neuron regeneration accuracy, and that the muscle pathway by itself is not the primary regulator for regeneration accuracy of motor neurons.