Motor cortex electrical stimulation promotes axon outgrowth to brain stem and spinal targets that control the forelimb impaired by unilateral corticospinal injury.
We previously showed that electrical stimulation of motor cortex (M1) after unilateral pyramidotomy in the rat increased corticospinal tract (CST) axon length, strengthened spinal connections, and restored forelimb function. Here, we tested: (i) if M1 stimulation only increases spinal axon length or if it also promotes connections to brain stem forelimb control centers, especially magnocellular red nucleus; and (ii) if stimulation-induced increase in axon length depends on whether pyramidotomy denervated the structure. After unilateral pyramidotomy, we electrically stimulated the forelimb area of intact M1, to activate the intact CST and other corticofugal pathways, for 10 days. We anterogradely labeled stimulated M1 and measured axon length using stereology. Stimulation increased axon length in both the spinal cord and magnocellular red nucleus, even though the spinal cord is denervated by pyramidotomy and the red nucleus is not. Stimulation also promoted outgrowth in the cuneate and parvocellular red nuclei. In the spinal cord, electrical stimulation caused increased axon length ipsilateral, but not contralateral, to stimulation. Thus, stimulation promoted outgrowth preferentially to the sparsely corticospinal-innervated and impaired side. Outgrowth resulted in greater axon density in the ipsilateral dorsal horn and intermediate zone, resembling the contralateral termination pattern. Importantly, as in spinal cord, increase in axon length in brain stem also was preferentially directed towards areas less densely innervated by the stimulated system. Thus, M1 electrical stimulation promotes increases in corticofugal axon length to multiple M1 targets. We propose the axon length change was driven by competition into an adaptive pattern resembling lost connections.
Departments of Neurology & Neuroscience and Pediatrics, Weill Cornell Medical College, New York, NY 10021, USA. jbc7001@med.cornell.edu
Jason B
JB
Carmel
Hiroki
H
Kimura
Lauren J
LJ
Berrol
John H
JH
Martin
D000818:Animals; D001369:Axons / Q000502:physiology; D001933:Brain Stem / Q000502:physiology*; D003714:Denervation; D004558:Electric Stimulation; D005260:Female; D005552:Forelimb / Q000294:innervation; D009044:Motor Cortex / Q000502:physiology*; D009416:Nerve Regeneration; D020671:Posterior Horn Cells / Q000502:physiology; D011712:Pyramidal Tracts / Q000293:injuries / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley