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Transgenic labeling of the corticospinal tract for monitoring axonal responses to spinal cord injury

Abstract

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.

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Figure 1: YFP expression is limited to the forebrain and CST in CST-YFP mice.
Figure 2: YFP expression in the spinal cord of CST-YFP mice.
Figure 3: Degeneration of CST axons and collaterals after lesion.
Figure 4: Reorganization of minor CST components after lesion of the dorsal CST component.

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Acknowledgements

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.

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Correspondence to Joshua R Sanes.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

YFP expression in the cortex. (PDF 873 kb)

Supplementary Fig. 2

Specificity of CST labeling in CST-YFP mice. (PDF 392 kb)

Supplementary Fig. 3

Development of CST projections in CST-YFP mice. (PDF 266 kb)

Supplementary Fig. 4

Contacts between minor CST fibers and motoneurons. (PDF 339 kb)

Supplementary Fig. 5

Reorganization of minor CST components after specific dorsal lesion. (PDF 257 kb)

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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). https://doi.org/10.1038/nm1331

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