Neuronal activity as a therapy for peripheral nerve injury Open Access

Jones, Laura (2014)

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Moderate daily exercise is an effective way to enhance axon regeneration and improve functional recovery from peripheral nerve injury. Increased neuronal activity associated with locomotion has been hypothesized to be the basis for this facilitation, but other factors also have been suggested. Neuronal activity can be produced separately from these other potential sources of enhancement of axon regeneration using optogenetics. We hypothesized that increased neural activity would be sufficient to promote axon regeneration after peripheral nerve transection. In mice that express a light-activated cation channel, channelrhodopsin2 (ChR2), and yellow fluorescent proteins (YFP) in neurons, we activated axons in the sciatic nerve using blue light immediately prior to transection and measured axon regeneration at three time points: two, three and four weeks post transection. By two weeks after injury, optical activation enhanced axon regeneration to the same extent as electrical stimulation. Treatments with brief electrical stimulation or optical activation just prior to nerve transection and repair both resulted in larger M responses three weeks later, but the optical treatment led to nearly exclusive enhancement of regeneration of axons which were ChR2+. By four weeks after sciatic nerve transection and repair, significant reinnervation of muscle fibers had occurred in all animals studied. In mice treated optically, all of the re-occupied motor end plates were ChR2+, consistent with selective enhancement of optically activatable motor axons. These anatomical observations are consistent with our hypothesis that increased neuronal activity is adequate to promote axon regeneration after peripheral nerve injury.

Table of Contents

Introduction 1

Materials and Methods 6

Results 13

Discussion 19

Figure Legends 25

References 27

Figures 32

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