Chemotropic guidance facilitates axonal regeneration and synapse formation after spinal cord injury

Laura Taylor Alto, Leif A. Havton, James M. Conner, Edmund R. Hollis, Armin Blesch, Mark H. Tuszynski

Research output: Contribution to journalArticle

157 Scopus citations

Abstract

A principal objective of spinal cord injury (SCI) research is the restoration of axonal connectivity to denervated targets. We tested the hypothesis that chemotropic mechanisms would guide regenerating spinal cord axons to appropriate brainstem targets. We subjected rats to cervical level 1 (C1) lesions and combinatorial treatments to elicit axonal bridging into and beyond lesion sites. Lentiviral vectors expressing neurotrophin-3 (NT-3) were then injected into an appropriate brainstem target, the nucleus gracilis, and an inappropriate target, the reticular formation. NT-3 expression in the correct target led to reinnervation of the nucleus gracilis in a dose-related fashion, whereas NT-3 expression in the reticular formation led to mistargeting of regenerating axons. Axons regenerating into the nucleus gracilis formed axodendritic synapses containing rounded vesicles, reflective of pre-injury synaptic architecture. Thus, we report for the first time, to the best of our knowledge, the reinnervation of brainstem targets after SCI and an essential role for chemotropic axon guidance in target selection.

Original languageEnglish (US)
Pages (from-to)1106-1113
Number of pages8
JournalNature neuroscience
Volume12
Issue number9
DOIs
StatePublished - Sep 2009

ASJC Scopus subject areas

  • Neuroscience(all)

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