title: Ryk controls remapping of motor cortex during functional recovery after spinal cord injury.
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.
authors.affiliation: Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, California, USA.
authors.forename: Edmund R
authors.identifier: http://orcid.org/0000-0002-4535-4668
authors.initials: ER
authors.lastname: Hollis
authors.affiliation: Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, California, USA.
authors.forename: Nao
authors.initials: N
authors.lastname: Ishiko
authors.affiliation: Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, California, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Yu
authors.affiliation: Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, California, USA.
authors.forename: Chin-Chun
authors.initials: CC
authors.lastname: Lu
authors.affiliation: Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, California, USA.
authors.forename: Ariela
authors.initials: A
authors.lastname: Haimovich
authors.affiliation: Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, California, USA.
authors.forename: Kristine
authors.initials: K
authors.lastname: Tolentino
authors.affiliation: Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, California, USA.
authors.forename: Alisha
authors.initials: A
authors.lastname: Richman
authors.affiliation: Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, California, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Tury
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors.forename: Shih-Hsiu
authors.initials: SH
authors.lastname: Wang
authors.affiliation: Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, California, USA.
authors.forename: Maysam
authors.initials: M
authors.lastname: Pessian
authors.affiliation: Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, California, USA.
authors.forename: Euna
authors.initials: E
authors.lastname: Jo
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Kolodkin
authors.affiliation: Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, California, USA.
authors.forename: Yimin
authors.identifier: http://orcid.org/0000-0002-1092-5547
authors.initials: Y
authors.lastname: Zou
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001931:Brain Mapping; D005081:Exercise Therapy; D005260:Female; D005552:Forelimb / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009044:Motor Cortex / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D011712:Pyramidal Tracts / Q000166:cytology / Q000187:drug effects; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000628:therapy
chemical_list: D000911:Antibodies, Monoclonal; D020794:Receptor Protein-Tyrosine Kinases; C118148:Ryk protein, mouse