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Translational Neuroscience

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Plasticity to neonatal sensorimotor cortex injury

Sarah Galley / Gavin Clowry
Published Online: 2010-10-12 | DOI: https://doi.org/10.2478/v10134-010-0011-1


A CST-YFP transgenic mouse has been developed for the study of the corticospinal tract in which yellow fluorescent protein is expressed under the control of thy1 and emx1 promoters in order to restrict expression to forebrain neurones. We explored plasticity of the developing corticospinal tract of these mice following a unilateral lesion to the sensorimotor cortex at postnatal day 7. The extent of innervation of the cervical spinal cord at time points post-lesion was assessed by measuring density of immunoperoxidase reactivity for yellow fluorescent protein in the dorsal funiculi and a defined region of each dorsal horn, and by counting immunoreactive axonal varicosities in the ventral horns. Two/three days post-lesion, the density of immunoreactivity in the dorsal horn contralateral to the lesion was reduced proportional to the decrease in positive fibres in the dorsal funiculus, however density of immunoreactive varicosities in the ventral horn was more resistant to loss. Over a three week period, immunoreactive axonal processes in the grey matter increased on the contralateral side, particularly in the ventral horn, but without an increase in immunopositive fibres in the contralateral dorsal funiculus, demonstrating sprouting of surviving immunoreactive fibres to replace lesioned corticospinal axons. However, the origin of sprouting fibres could not be identified with confidence as parallel observations revealed strongly immunoreactive neuronal cell bodies in the spinal cord, medulla and red nucleus. We have demonstrated plasticity in response to a developmental lesion but discovered a drawback to using these mice if visualisation of individual axons is enhanced by immunohistochemistry.

Keywords: Cerebral palsy; Corticospinal system; Development; Spinal cord injury; Stroke; Transgenic mouse

  • [1] Reinoso B.S., Castro A.J. A study of corticospinal remodelling using fluorescent retrograde tracers in rats. Exp. Brain Res., 1989, 74, 387–394. http://dx.doi.org/10.1007/BF00248872CrossrefGoogle Scholar

  • [2] Kuang R.Z., Kalil, K. Specificity of corticospinal axon arbours sprouting into denervated contralateral spinal cord. J. Comp. Neurol., 1990, 302, 461–472. http://dx.doi.org/10.1002/cne.903020304CrossrefGoogle Scholar

  • [3] Rouiller E.M., Liang F., Moret V., Weisendanger M. Trajectory of redirected corticospinal axons after unilateral lesions of the sensorimotor cortex in neonatal rat; a phaseolus vulgaris-leucoagglutinin (PHA-L) tracing study. Exp. Neurol., 1991, 114, 53–65. http://dx.doi.org/10.1016/0014-4886(91)90084-PCrossrefGoogle Scholar

  • [4] Stanfield, B.B. The development of the corticospinal projection. Prog. Neurobiol., 1992, 38, 169–202. http://dx.doi.org/10.1016/0301-0082(92)90039-HCrossrefGoogle Scholar

  • [5] Clowry G.J., Davies B.M., Upile N.S., Gibson C.L., Bradley P.M. Spinal cord plasticity in response to unilateral inhibition of the rat motor cortex during development: changes to gene expression, muscle afferents and the ipsilateral corticospinal projection. Eur. J. Neurosci., 2004, 20, 2555–2566. http://dx.doi.org/10.1111/j.1460-9568.2004.03713.xCrossrefGoogle Scholar

  • [6] Martin J.H., Kably B., Hacking A. Activity-dependent development of cortical axon terminations in the spinal cord and brainstem. Exp. Brain Res., 1999, 125, 184–199. http://dx.doi.org/10.1007/s002210050673CrossrefGoogle Scholar

  • [7] Eyre J.A., Smith M., Dabydeen L., Clowry G.J., Petacchi E., Battini R., et al. Is hemiplegic cerebral palsy equivalent to amblyopia of the corticospinal system? Annal. Neurol., 2007, 62, 493–503. http://dx.doi.org/10.1002/ana.21108Web of ScienceCrossrefGoogle Scholar

  • [8] Basu A., Graziadio S., Smith M., Clowry G.J., Cioni G., Eyre J.A. Developmental plasticity connects visual cortex to motoneurons after stroke. Annal. Neurol., 2010, 67, 132–136. http://dx.doi.org/10.1002/ana.21827Web of ScienceCrossrefGoogle Scholar

  • [9] Aisaka A., Aimi Y., Yasuhara O., Tooyama I., Kimura H., Shimada M. Two modes of corticospinal reinnervation occur close to spinal targets following unilateral lesion of the motor cortex in neonatal hamsters. Neuroscience, 1999, 90, 53–67. http://dx.doi.org/10.1016/S0306-4522(98)00424-2CrossrefGoogle Scholar

  • [10] Salimi I., Friel K.M., Martin J. H. Pyramidal tract stimulation restores normal corticospinal tract connections and visuomotor skill after early postnatal motor cortex activity blockade. J. Neurosci., 2008, 28, 7426–7434. http://dx.doi.org/10.1523/JNEUROSCI.1078-08.2008Web of ScienceCrossrefGoogle Scholar

  • [11] Joosten E. A. J., Van Eden C. G. An anterograde tracer study on the development of corticospinal projections from the medial prefrontal cortex in the rat. Dev. Brain Res., 1989, 45, 313–319. http://dx.doi.org/10.1016/0165-3806(89)90051-5CrossrefGoogle Scholar

  • [12] Oudega M., Varon S., Hagg T. Distribution of corticospinal motor neurons in the postnatal rat: quantitative evidence for massive collateral elimination and modest cell death. J. Comp. Neurol., 1994, 347, 115–126. http://dx.doi.org/10.1002/cne.903470109CrossrefGoogle Scholar

  • [13] Low L.K., Liu X-B., Faulkner R. L., Coble J., Cheng H-J. Plexin signaling selectively regulates the stereotyped pruning of corticospinal axons from visual cortex. Proc. Natl. Acad. Sci. USA, 2008, 105, 8136–8141. http://dx.doi.org/10.1073/pnas.0803849105CrossrefGoogle Scholar

  • [14] Bareyre F. M., Kerschensteiner M., Misgeld T., Sanes J. R. Transgenic labeling of the corticospinal tract for monitoring axonal responses to spinal cord injury. Nature Med., 2005, 11, 1355–1360. http://dx.doi.org/10.1038/nm1331CrossrefGoogle Scholar

  • [15] Liu Z, Zhang RL, Li Y, Cui Y, Chopp M. Remodeling of the corticospinal innervation and spontaneous behavioral recovery after ischemic stroke in adult mice. Stroke, 2009, 40, 2546–2551. http://dx.doi.org/10.1161/STROKEAHA.109.547265CrossrefWeb of ScienceGoogle Scholar

  • [16] 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., 2004, 472, 463–477. http://dx.doi.org/10.1002/cne.20090CrossrefGoogle Scholar

  • [17] Brösamle C., Schwab, M.E. Ipsilateral, ventral corticospinal tract of the adult rat: ultrastructure, myelination and synaptic connections. J. Neurocytol., 2000, 499–507. CrossrefGoogle Scholar

  • [18] Antal, M., Sholomenko, G.N., Moschovakis, A.K., Storm-Mathisen, J., Eximan, C.W., Hunziker, W. The termination pattern and postsynaptic targets of rubrospinal fibers in the rat spinal cord: a light and electron microscopic study. J. Comp. Neurol., 1992, 325, 22–37. http://dx.doi.org/10.1002/cne.903250103CrossrefGoogle Scholar

  • [19] Gianino S., Stein S.A., Li H., Lu X., Biesiada E., Ulas J, et al. Postnatal growth of corticospinal axons in the spinal cord of developing mice. Dev. Brain Res. 1999, 112: 189–204. http://dx.doi.org/10.1016/S0165-3806(98)00168-0CrossrefGoogle Scholar

  • [20] Kamiyama, T., Yoshioka, N., Sakurai, M. Synapse elimination in the corticospinal projection during the early postnatal period. J. Neurophysiol., 2006, 95, 2304–2313. http://dx.doi.org/10.1152/jn.00295.2005CrossrefGoogle Scholar

  • [21] Gorski J.A., Talley T., Qiu M., Puelles L., Rubenstein J.L.R., Jones K.R. Cortical excitatory neurons and glia, but not gabaergic neurons, are produced in the emx1-expressing lineage. J. Neurosci., 2002, 22, 6309–6314. Google Scholar

  • [22] Lemon R.N. Descending pathways in motor control. Ann. Rev. Neurosci., 2008, 31, 195–218.rain http://dx.doi.org/10.1146/annurev.neuro.31.060407.125547CrossrefGoogle Scholar

  • [23] Kuchler M, Fouad K, Weinmann O, Schwab ME, Raineteau O. Red nucleus projections to distinct motor neuron pools in the rat spinal cord. J. Comp. Neurol., 2002, 448, 349–359. http://dx.doi.org/10.1002/cne.10259CrossrefGoogle Scholar

  • [24] Al-Izki S., Kirkwood P.A., Lemon R.N., Denton, M.E. Electrophysiological actions of the rubrospinal tract in the anaesthetised rat. Exp. Neurol., 2008, 212, 118–131. http://dx.doi.org/10.1016/j.expneurol.2008.03.020Web of ScienceCrossrefGoogle Scholar

  • [25] Belhaj-Saif, A., Cheney, P.D. Plasticity in the distribution of the red nucleus output to forearm muscles after unilateral lesions of the pyramidal tract. J. Neurophysiol., 2000, 83, 3147–3153. Google Scholar

  • [26] Joosten E. A. J., Schuitman R. L., Vermelis M. E, J., Dederen P. J. W. C. Postnatal development of the ipsilateral corticospinal component in rat spinal cord: a light and electron microscopic anterograde HRP study. J. Comp. Neurol., 1992, 324, 133–146. http://dx.doi.org/10.1002/cne.903260112CrossrefGoogle Scholar

  • [27] Uematsu J., Ono K., Yamano K., Shimada M. Development of corticospinal tract fibers and their plasticity II. Neonatal unilateral cortical damage and subsequent development of the corticospinal tract in mice. Brain Dev., 1996, 18, 173–178. http://dx.doi.org/10.1016/0387-7604(95)00152-2CrossrefGoogle Scholar

  • [28] Hsu J-Y. C., Stein S.A., Xua X-M. Development of the corticospinal tract in the mouse spinal cord: A quantitative ultrastructural analysis. Brain Res., 2006, 1084, 16–27. http://dx.doi.org/10.1016/j.brainres.2006.02.036CrossrefGoogle Scholar

  • [29] Li C-P, Olavarria J.F., Greger B.E. Occipital cortico-pyramidal projection in hypothyroid rats. Dev. Brain Res., 1995, 227–234. CrossrefGoogle Scholar

  • [30] Gibson, C.L., Arnott, G.A., Clowry, G.J. Plasticity in the rat spinal cord seen in response to lesions to the motor cortex during development but not to lesions in maturity. Exp Neurol., 2000, 166, 422–434. http://dx.doi.org/10.1006/exnr.2000.7511CrossrefGoogle Scholar

  • [31] Clowry, G. J. The dependence of spinal cord development on corticospinal input and its significance in understanding and treating spastic cerebral palsy. Neurosci. Biobehav. Rev., 2007, 31, 1114–1124. http://dx.doi.org/10.1016/j.neubiorev.2007.04.007Web of ScienceCrossrefGoogle Scholar

  • [32] O’sullivan M.C., Miller S., Ramesh V., Conway E., Gilfillan K., McDonough S., et al. Abnormal development of biceps brachii phasic stretch reflex and persistence of short latency heteronymous reflexes from biceps to triceps brachii in spastic cerebral palsy. Brain, 1998, 121, 2381–2395. http://dx.doi.org/10.1093/brain/121.12.2381CrossrefGoogle Scholar

  • [33] Martin JH, Lee S. 1999. Activity-dependent competition between developing corticospinal terminations. Neuroreport, 1999, 10, 2277–82. http://dx.doi.org/10.1097/00001756-199908020-00010CrossrefGoogle Scholar

About the article

Published Online: 2010-10-12

Published in Print: 2010-03-01

Citation Information: Translational Neuroscience, Volume 1, Issue 1, Pages 16–23, ISSN (Online) 2081-6936, ISSN (Print) 2081-3856, DOI: https://doi.org/10.2478/v10134-010-0011-1.

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© 2010 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

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