title: Functional redundancy of ventral spinal locomotor pathways.
abstract: Identification of long tracts responsible for the initiation of spontaneous locomotion is critical for spinal cord injury (SCI) repair strategies. Pathways derived from the mesencephalic locomotor region and pontomedullary medial reticular formation responsible for fictive locomotion in decerebrate preparations project to the thoracolumbar levels of the spinal cord via reticulospinal axons in the ventrolateral funiculus (VLF). However, white matter regions critical for spontaneous over-ground locomotion remain unclear because cats, monkeys, and humans display varying degrees of locomotor recovery after ventral SCIs. We studied the contributions of myelinated tracts in the VLF and ventral columns (VC) to spontaneous over-ground locomotion in the adult rat using demyelinating lesions. Animals received ethidium bromide plus photon irradiation producing discrete demyelinating lesions sufficient to stop axonal conduction in the VLF, VC, VLF-VC, or complete ventral white matter (CV). Behavior [open-field Basso, Beattie, and Bresnahan (BBB) scores and grid walking] and transcranial magnetic motor-evoked potentials (tcMMEP) were studied at 1, 2, and 4 weeks after lesion. VLF lesions resulted in complete loss or severe attenuation of tcMMEPs, with mean BBB scores of 18.0, and no grid walking deficits. VC lesions produced behavior similar to VLF-lesioned animals but did not significantly affect tcMMEPs. VC-VLF and CV lesions resulted in complete loss of tcMMEP signals with mean BBB scores of 12.7 and 6.5, respectively. Our data support a diffuse arrangement of axons within the ventral white matter that may comprise a system of multiple descending pathways subserving spontaneous over-ground locomotion in the intact animal.
authors.affiliation: The MD/PhD Program and Department of Neurological Surgery, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA.
authors.forename: David N
authors.initials: DN
authors.lastname: Loy
authors.forename: David S K
authors.initials: DS
authors.lastname: Magnuson
authors.forename: Y Ping
authors.initials: YP
authors.lastname: Zhang
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Onifer
authors.forename: Michael D
authors.initials: MD
authors.lastname: Mills
authors.forename: Qi-lin
authors.initials: QL
authors.lastname: Cao
authors.forename: Jessica B
authors.initials: JB
authors.lastname: Darnall
authors.forename: Lily C
authors.initials: LC
authors.lastname: Fajardo
authors.forename: Darlene A
authors.initials: DA
authors.lastname: Burke
authors.forename: Scott R
authors.initials: SR
authors.lastname: Whittemore
mesh_terms: D000818:Animals; D000870:Anterior Horn Cells / Q000187:drug effects / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology; D002452:Cell Count; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000503:physiopathology; D004996:Ethidium; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005260:Female; D006614:Hindlimb / Q000294:innervation / Q000502:physiology / Q000503:physiopathology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D015225:Magnetoencephalography; D008636:Mesencephalon / Q000502:physiology; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D010315:Particle Accelerators; D010777:Photochemistry; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D012680:Sensitivity and Specificity; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
chemical_list: D004996:Ethidium