Journal Article

Intrinsic neuronal properties control selective targeting of regenerating motoneurons

Colin K. Franz, Urs Rutishauser and Victor F. Rafuse

in Brain

Published on behalf of The Guarantors of Brain

Volume 131, issue 6, pages 1492-1505
Published in print June 2008 | ISSN: 0006-8950
Published online March 2008 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awn039
Intrinsic neuronal properties control selective targeting of regenerating motoneurons

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Despite advances in microsurgical techniques, recovery of motor function after peripheral nerve injury is often poor because many regenerating axons reinnervate inappropriate targets. Consequently, surgical repair must include treatment strategies that improve motor axon targeting. Development of such treatments will require a better understanding of the molecular mechanisms governing selective motor axon targeting. This study used a well-established model of nerve transection and repair to examine (1) whether intrinsic differences exist between different pools of motoneurons after peripheral nerve injury, (2) if such differences regulate selective axon targeting, (3) if regenerating motor axons must express polysialic acid (PSA) in order to preferentially reinnervate muscle and (4) whether brief electrical stimulation improves regeneration accuracy because it increases PSA expression on regenerating axons. We found that different motor pools differentially express PSA after injury and that the capacity to re-express PSA appears to be an intrinsic neuronal property established during development. Second, motoneuron pools not up-regulating PSA did not preferentially reinnervate muscle after injury. Third, brief electrical stimulation of the proximal nerve stump immediately after injury only improved selective motor axon targeting if the motoneurons were capable of up-regulating PSA. Finally, the benefits of stimulation were completely abolished if PSA was removed from the regenerating axons. These results indicate that (1) intrinsic neuronal differences between motor pools must be considered in the development of treatments designed to improve axon targeting and (2) therapeutics aimed at increasing PSA levels on regenerating motor axons may lead to superior functional outcomes.

Keywords: axon guidance; sprouting; NCAM; polysialic acid; electrical stimulation

Journal Article.  9104 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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