Ryk controls remapping of motor cortex during functional recovery after spinal cord injury

Edmund R. Hollis, Nao Ishiko, Ting Yu, Chin Chun Lu, Ariela Haimovich, Kristine Tolentino, Alisha Richman, Anna Tury, Shih Hsiu Wang, Maysam Pessian, Euna Jo, Alex L Kolodkin, Yimin Zou

Research output: Contribution to journalArticle

Abstract

Limited functional recovery can be achieved through rehabilitation after incomplete spinal cord injury. Eliminating the function of a repulsive Wnt receptor, Ryk, in mice and rats by either conditional knockout in the motor cortex or monoclonal antibody infusion resulted in increased corticospinal axon collateral branches with presynaptic puncta in the spinal cord and enhanced recovery of forelimb reaching and grasping function following a cervical dorsal column lesion. Using optical stimulation, we observed that motor cortical output maps underwent massive changes after injury and that hindlimb cortical areas were recruited to control the forelimb over time. Furthermore, a greater cortical area was dedicated to controlling the forelimb in Ryk conditional knockout mice than in controls (wild-Type or heterozygotes). In the absence of weekly task-specific training, recruitment of ectopic cortical areas was greatly reduced and there was no significant functional recovery even in Ryk conditional knockout mice. Our study provides evidence that maximal circuit reorganization and functional recovery can be achieved by combining molecular manipulation and targeted rehabilitation.

Original languageEnglish (US)
Pages (from-to)697-705
Number of pages9
JournalNature Neuroscience
Volume19
Issue number5
DOIs
StatePublished - May 1 2016

ASJC Scopus subject areas

  • Neuroscience(all)

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    Hollis, E. R., Ishiko, N., Yu, T., Lu, C. C., Haimovich, A., Tolentino, K., Richman, A., Tury, A., Wang, S. H., Pessian, M., Jo, E., Kolodkin, A. L., & Zou, Y. (2016). Ryk controls remapping of motor cortex during functional recovery after spinal cord injury. Nature Neuroscience, 19(5), 697-705. https://doi.org/10.1038/nn.4282