Regenerating motor bridge axons refine connections and synapse on lumbar motoneurons to bypass chronic spinal cord injury.
To restore motor control after spinal cord injury requires reconnecting the brain with spinal motor circuits below the lesion. A bridge around the injury is an important alternative to promoting axon regeneration through the injury. Previously, we reported a novel motor bridge in rats. The thirteenth thoracic nerve was detached from the muscle it innervates and the cut end implanted caudally into the lumbar gray matter where motor bridge axons regenerate. In this study, we first determined that regenerating bridge axons project to spinal motor circuits. Stable projections were present in ventral motor laminae of the cord, including putative synapses directly on motoneurons, 2 months after insertion in the intact cord. At this time, earlier-forming dorsal horn projections were mostly eliminated. Regenerating axons were effective in evoking leg motor activity as early as 2 weeks. We next determined that bridge axons could regenerate caudal to a chronic injury. We hemisected the spinal cord at L2 and inserted the bridge nerve 1 month later at L5 and found ventral laminae projections similar to those in intact animals, including onto motoneurons directly. Finally, we determined that the bridge circuit could be activated by neural pathways rostral to its origin. For spinally hemisected animals, we electrically stimulated the rostral spinal cord and recorded evoked potentials from the bridge and, in turn, motor responses in the sciatic nerve. Our findings suggests that bridge motoneurons could be used by descending motor pathways as premotor interneurons to transmit neural signals to bypass a chronic spinal injury.
Campos
Lucas W
LW
Department of Neuroscience, Columbia University, New York, New York 10032, USA.
Chakrabarty
Samit
S
Haque
Raqeeb
R
Martin
John H
JH
D000009:Abdominal Muscles / Q000294:innervation; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology / Q000637:transplantation; D004558:Electric Stimulation; D005260:Female; D008159:Lumbar Vertebrae; D009046:Motor Neurons / Q000502:physiology / Q000637:transplantation*; D009416:Nerve Regeneration / Q000502:physiology*; D009434:Neural Pathways / Q000166:cytology / Q000254:growth & development*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000534:rehabilitation* / Q000601:surgery; D013569:Synapses / Q000502:physiology; D013900:Thoracic Nerves / Q000166:cytology / Q000254:growth & development* / Q000637:transplantation