title: Both dorsal and ventral spinal cord pathways contribute to overground locomotion in the adult rat.
abstract: Identification of long tracts responsible for spontaneous locomotion is critical for spinal cord injury (SCI) repair strategies. We recently demonstrated that extensive demyelination of adult rat thoracic ventral columns, ventromedial, and ventrolateral white matter produces persistent, significant open-field hindlimb locomotor deficits. Locomotor movements resulting from stimulation of the pontomedullary locomotor region are inhibited by dorsolateral funiculus (DLF) lesions suggesting that important pathways for locomotion may also exist in the dorsal white matter. However, dorsal hemisections that interrupt dorsal columns/dorsal corticospinal tract (DC/CST) and DLF pathways do not produce persistent, severe locomotor deficits in the adult rat. We studied the contributions of myelinated tracts in the DLF and DC/CST to overground locomotion following complete conduction blockade of axons in the ventrolateral funiculus (VLF), a region important for locomotor movements and for transcranial magnetic motor-evoked potentials (tcMMEP). Animals received ethidium bromide plus photon irradiation to produce discrete demyelinating lesions sufficient to stop axonal conduction in the VLF, combined VLF + DLF, or combined VLF + DC/CST. Open-field BBB scores and tcMMEPs were studied at 1, 2, 3, and 4 weeks postlesion. VLF lesions resulted in mean BBB scores of 17 at 4 weeks. VLF + DC/CST and VLF + DLF lesions resulted in mean BBB scores of 15.9 and 11.1, respectively. TcMMEPs were absent in all lesion types confirming VLF conduction blockade throughout the study. Our data indicate that significant contributions to locomotion from myelinated pathways within the rat DLF can be revealed when combined with simultaneous compromise of the VLF.
authors.affiliation: MD/PhD Program, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA.
authors.forename: David N
authors.initials: DN
authors.lastname: Loy
authors.forename: Jason F
authors.initials: JF
authors.lastname: Talbott
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Onifer
authors.forename: Michael D
authors.initials: MD
authors.lastname: Mills
authors.forename: Darlene A
authors.initials: DA
authors.lastname: Burke
authors.forename: Jessica B
authors.initials: JB
authors.lastname: Dennison
authors.forename: Lili C
authors.initials: LC
authors.lastname: Fajardo
authors.forename: David S K
authors.initials: DS
authors.lastname: Magnuson
authors.forename: Scott R
authors.initials: SR
authors.lastname: Whittemore
mesh_terms: D000818:Animals; D000870:Anterior Horn Cells / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D001369:Axons / Q000502:physiology; D004525:Efferent Pathways / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D004558:Electric Stimulation / Q000295:instrumentation; D004574:Electromagnetic Fields; D004996:Ethidium / Q000494:pharmacology; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006614:Hindlimb / Q000294:innervation / Q000502:physiology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009186:Myelin Sheath / Q000187:drug effects / Q000528:radiation effects; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009431:Neural Conduction / Q000187:drug effects / Q000528:radiation effects; D020671:Posterior Horn Cells / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051381:Rats; D011916:Rats, Inbred F344; D020127:Recovery of Function; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
chemical_list: D004996:Ethidium