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Rewiring of hindlimb corticospinal neurons after spinal cord injury

Nature Neuroscience volume 13, pages 97–104 (2010)Cite this article

Abstract

Little is known about the functional role of axotomized cortical neurons that survive spinal cord injury. Large thoracic spinal cord injuries in adult rats result in impairments of hindlimb function. Using retrograde tracers, we found that axotomized corticospinal axons from the hindlimb sensorimotor cortex sprouted in the cervical spinal cord. Mapping of these neurons revealed the emergence of a new forelimb corticospinal projection from the rostral part of the former hindlimb cortex. Voltage-sensitive dye (VSD) imaging and blood-oxygen-level–dependent functional magnetic resonance imaging (BOLD fMRI) revealed a stable expansion of the forelimb sensory map, covering in particular the former hindlimb cortex containing the rewired neurons. Therefore, axotomised hindlimb corticospinal neurons can be incorporated into the sensorimotor circuits of the unaffected forelimb.

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Figure 1: Behavioral analysis after a thoracic spinal cord injury.
Figure 2: Retrograde labeling of hindlimb corticospinal neurons projecting to the cervical spinal cord gray matter.
Figure 3: BOLD-fMRI mapping of forelimb activation in the sensory motor cortex before and after injury.
Figure 4: Voltage-sensitive dye imaging of the sensory and motor cortices responding to forelimb stimulation before and after injury.
Figure 5: Response of the hindlimb sensorimotor cortex to forelimb stimulation in intact and injured rats.
Figure 6: Forelimb stimulation evoked action potentials in the corticospinal tract at thoracic level T7.

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Acknowledgements

We thank J. Scholl, E. Hochreutener, R. Schöb and L. Schnell for technical assistance. We thank A. Buchli, I. Maier, M. Starkey, V. Pernet, D. Margolis and B. Kampa for helpful discussions. This work was supported by the Swiss National Science Foundation, Grant 31–63633.00, the National Center of Competence in Research “Neural Plasticity and Repair” of the Swiss National Science Foundation, the Spinal Cord Consortium of the Christopher Reeve Paralysis Foundation, and NeuroNe, Network of Excellence of the European Consortium for Research in Neurodegenerative Diseases (Sixth Framework EU Program).

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  1. Arko Ghosh

    Present address: Present address: Institute of Neuroinformatics, University of Zurich and Swiss Federal Institute of Technology Zurich, Zurich, Switzerland.,

Authors and Affiliations

  1. Brain Research Institute, University of Zurich and Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

    Arko Ghosh, Regula Schneider, Miriam Gullo & Martin E Schwab

  2. Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland

    Florent Haiss, Matthias T Wyss, Markus Rudin & Bruno Weber

  3. Institute for Biomedical Engineering, University of Zurich and Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

    Esther Sydekum, Thomas Mueggler, Christof Baltes & Markus Rudin

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Contributions

A.G. and M.E.S. designed the experiments and prepared the manuscript. A.G., F.H. and E.S. carried out and interpreted the experiments. R.S., M.G., M.T.W., T.M. and C.B. performed the experiments. M.R. and B.W. prepared the manuscript.

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Correspondence to Arko Ghosh.

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Ghosh, A., Haiss, F., Sydekum, E. et al. Rewiring of hindlimb corticospinal neurons after spinal cord injury. Nat Neurosci 13, 97–104 (2010). https://doi.org/10.1038/nn.2448

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