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The Journal of Neuroscience, December 12, 2007, 27(50):13793-13801; doi:10.1523/JNEUROSCI.3489-07.2007

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Development/Plasticity/Repair
Electrical Stimulation of Spared Corticospinal Axons Augments Connections with Ipsilateral Spinal Motor Circuits after Injury

Marcel Brus-Ramer,¹ Jason B. Carmel,^1,2 Samit Chakrabarty,¹ and John H. Martin^1,3,4

Departments of ¹Neuroscience, ²Neurology, ³Neurological Surgery, and ⁴Psychiatry, Columbia University and New York State Psychiatric Institute, New York, New York 10032

Correspondence should be addressed to Dr. John H. Martin, Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032. Email: jm17{at}columbia.edu

Activity-dependent competition shapes corticospinal (CS) axon outgrowth in the spinal cord during development. An important question in neural repair is whether activity can be used to promote outgrowth of CS axons in maturity. After injury, spared CS axons sprout and make new connections, but often not enough to restore function. We propose that electrically stimulating spared axons after injury will enhance sprouting and strengthen connections with spinal motor circuits. To study the effects of activity, we electrically stimulated CS tract axons in the medullary pyramid. To study the effects of injury, one pyramid was lesioned. We studied sparse ipsilateral CS projections of the intact pyramid as a model of the sparse connections preserved after CNS injury. We determined the capacity of CS axons to activate ipsilateral spinal motor circuits and traced their spinal projections. To understand the separate and combined contributions of injury and activity, we examined animals receiving stimulation only, injury only, and injury plus stimulation. Both stimulation and injury alone strengthened CS connectivity and increased outgrowth into the ipsilateral gray matter. Stimulation of spared axons after injury promoted outgrowth that reflected the sum of effects attributable to activity and injury alone. CS terminations were densest within the ventral motor territories of the cord, and connections in these animals were significantly stronger than after injury alone, indicating that activity augments injury-induced plasticity. We demonstrate that activity promotes plasticity in the mature CS system and that the interplay between activity and injury preferentially promotes connections with ventral spinal motor circuits.

Key words: corticospinal; spinal motor circuits; motor cortex; plasticity; spinal cord injury; sprouting

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Received Aug. 1, 2007; revised Aug. 30, 2007; accepted Sept. 25, 2007.

Correspondence should be addressed to Dr. John H. Martin, Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032. Email: jm17{at}columbia.edu

Related articles in J. Neurosci.:

Strengthening Corticospinal Connections with Chronic Electrical Stimulation after Injury

Alain Frigon, Sergiy Yakovenko, Valeriya Gritsenko, Marie-Ève Tremblay, and Gregory Barrière
J. Neurosci. 2008 28: 3262-3263. [Full Text]  

This article has been cited by other articles:

				A. Frigon, S. Yakovenko, V. Gritsenko, M.-E. Tremblay, and G. Barriere Strengthening Corticospinal Connections with Chronic Electrical Stimulation after Injury J. Neurosci., March 26, 2008; 28(13): 3262 - 3263. [Full Text] [PDF]

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