The rodent corticospinal tract (CST) has been used extensively to investigate regeneration and remodeling of central axons after injury. CST axons are currently visualized after injection of tracer dye, which is invasive, incomplete and prone to variation, and often does not show functionally crucial but numerically minor tract components. Here, we characterize transgenic mice in which CST fibers are specifically and completely labeled by yellow fluorescent protein (YFP). Using these CST-YFP mice, we show that minor CST components are responsible for most monosynaptic contacts onto motoneurons. Lesions of the main dorsal CST lead to extension of new collaterals, some of them originating from large, heavily myelinated axons within the minor dorsolateral and ventral CST components. Some of these new collaterals form additional direct synapses onto motoneurons. We propose that CST-YFP mice will be useful for evaluating strategies designed to maximize such remodeling and to promote regeneration.
Subscribe to Journal
Get full journal access for 1 year
only $18.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Kalil, K. & Reh, T. A light and electron microscopic study of regrowing pyramidal tract fibers. J. Comp. Neurol. 211, 265–275 (1982).
Kuang, R.Z. & Kalil, K. Specificity of corticospinal axon arbors sprouting into denervated contralateral spinal cord. J. Comp. Neurol. 302, 461–472 (1990).
Schnell, L., Schneider, R., Kolbeck, R., Barde, Y.A. & Schwab, M.E. Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion. Nature 367, 170–173 (1994).
Terashima, T. Anatomy, development and lesion-induced plasticity of rodent corticospinal tract. Neurosci. Res. 22, 139–161 (1995).
Bregman, B.S. et al. Recovery from spinal cord injury mediated by antibodies to neurite growth inhibitors. Nature 378, 498–501 (1995).
Cheng, H., Cao, Y. & Olson, L. Spinal cord repair in adult paraplegic rats: partial restoration of hind limb function. Science 273, 510–513 (1996).
Li, Y., Field, P.M. & Raisman, G. Repair of adult rat corticospinal tract by transplants of olfactory ensheathing cells. Science 277, 2000–2002 (1997).
Weidner, N., Ner, A., Salimi, N. & Tuszynski, M.H. Spontaneous corticospinal axonal plasticity and functional recovery after adult central nervous system injury. Proc. Natl. Acad. Sci. USA 98, 3513–3518 (2001).
Bareyre, F.M., Haudenschild, B. & Schwab, M.E. Long-lasting sprouting and gene expression changes induced by the monoclonal antibody IN-1 in the adult spinal cord. J. Neurosci. 22, 7097–7110 (2002).
Bareyre, F.M. et al. The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats. Nat. Neurosci. 7, 269–277 (2004).
Demjen, D. et al. Neutralization of CD95 ligand promotes regeneration and functional recovery after spinal cord injury. Nat. Med. 10, 389–395 (2004).
Daston, M.M., Bastmeyer, M., Rutishauser, U. & O'Leary, D.D. Spatially restricted increase in polysialic acid enhances corticospinal axon branching related to target recognition and innervation. J. Neurosci. 16, 5488–5497 (1996).
Joosten, E.A., Gribnau, A.A. & Dederen, P.J. An anterograde tracer study of the developing corticospinal tract in the rat: three components. Brain Res. 433, 121–130 (1987).
Stanfield, B.B. The development of the corticospinal projection. Prog. Neurobiol. 38, 169–202 (1992).
Gianino, S. et al. Postnatal growth of corticospinal axons in the spinal cord of developing mice. Brain Res. Dev. Brain Res. 112, 189–204 (1999).
Martin, J.H. The corticospinal system: from development to motor control. Neuroscientist 11, 161–173 (2005).
Terashima, T., Ochiishi, T. & Yamauchi, T. Immunohistochemical detection of calcium/calmodulin-dependent protein kinase II in the spinal cord of the rat and monkey with special reference to the corticospinal tract. J. Comp. Neurol. 340, 469–479 (1994).
Steward, O., Zheng, B., Ho, C., Anderson, K. & Tessier-Lavigne, M. The dorsolateral corticospinal tract in mice: an alternative route for corticospinal input to caudal segments following dorsal column lesions. J. Comp. Neurol. 472, 463–477 (2004).
Brosamle, C. & Schwab, M.E. Cells of origin, course, and termination patterns of the ventral, uncrossed component of the mature rat corticospinal tract. J. Comp. Neurol. 386, 293–303 (1997).
Kerschensteiner, M., Schwab, M.E., Lichtman, J.W. & Misgeld, T. In vivo imaging of axonal degeneration and regeneration in the injured spinal cord. Nat. Med. 11, 572–577 (2005).
Pan, Y.A., Misgeld, T., Lichtman, J.W. & Sanes, J.R. Effects of neurotoxic and neuroprotective agents on peripheral nerve regeneration assayed by time-lapse imaging in vivo. J. Neurosci. 23, 11479–11488 (2003).
Buffelli, M. et al. Genetic evidence that relative synaptic efficacy biases the outcome of synaptic competition. Nature 424, 430–434 (2003).
Gorski, J.A. et al. Cortical excitatory neurons and glia, but not GABAergic neurons, are produced in the Emx1-expressing lineage. J. Neurosci. 22, 6309–6314 (2002).
Nudo, R.J. & Masterton, R.B. Descending pathways to the spinal cord, III: Sites of origin of the corticospinal tract. J. Comp. Neurol. 296, 559–583 (1990).
Steward, O., Zheng, B. & Tessier-Lavigne, M. False resurrections: distinguishing regenerated from spared axons in the injured central nervous system. J. Comp. Neurol. 459, 1–8 (2003).
Lichtman, J.W. & Sanes, J.R. Watching the neuromuscular junction. J. Neurocytol. 32, 767–775 (2003).
DeLuca, G.C., Ebers, G.C. & Esiri, M.M. Axonal loss in multiple sclerosis: a pathological survey of the corticospinal and sensory tracts. Brain 127, 1009–1018 (2004).
Kerschensteiner, M. et al. Remodeling of axonal connections contributes to recovery in an animal model of multiple sclerosis. J. Exp. Med. 200, 1027–1038 (2004).
Yin, H. et al. Combined MR spectroscopic imaging and diffusion tensor MRI visualizes corticospinal tract degeneration in amyotrophic lateral sclerosis. J. Neurol. 251, 1249–1254 (2004).
Feng, G. et al. Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28, 41–51 (2000).
F.M.B. was supported in part by a Young Investigator Fellowship from the Swiss National Science Foundation. M.K. and T.M. are supported by grants from the German National Science Foundation and the Christopher Reeve Paralysis Foundation. J.R.S. is supported by grants from the McDonnell Foundation and the US National Institutes of Health.
The authors declare no competing financial interests.
YFP expression in the cortex. (PDF 873 kb)
Specificity of CST labeling in CST-YFP mice. (PDF 392 kb)
Development of CST projections in CST-YFP mice. (PDF 266 kb)
Contacts between minor CST fibers and motoneurons. (PDF 339 kb)
Reorganization of minor CST components after specific dorsal lesion. (PDF 257 kb)
About this article
Cite this article
Bareyre, F., Kerschensteiner, M., Misgeld, T. et al. Transgenic labeling of the corticospinal tract for monitoring axonal responses to spinal cord injury. Nat Med 11, 1355–1360 (2005) doi:10.1038/nm1331
Neural Plasticity (2019)
Regeneration of Spinal Cord Connectivity Through Stem Cell Transplantation and Biomaterial Scaffolds
Frontiers in Cellular Neuroscience (2019)
Molecular Brain (2019)
Neuropilin-1-mediated pruning of corticospinal tract fibers is required for motor recovery after spinal cord injury
Cell Death & Disease (2019)
Differential innervation within a transverse plane of spinal gray matter by sensorimotor cortices, with special reference to the somatosensory cortices
Journal of Comparative Neurology (2019)