title: Corticospinal tract development and spinal cord innervation differ between cervical and lumbar targets.
abstract: The corticospinal (CS) tract is essential for voluntary movement, but what we know about the organization and development of the CS tract remains limited. To determine the total cortical area innervating the seventh cervical spinal cord segment (C7), which controls forelimb movement, we injected a retrograde tracer (fluorescent microspheres) into C7 such that it would spread widely within the unilateral gray matter (to >80%), but not to the CS tract. Subsequent detection of the tracer showed that, in both juvenile and adult mice, neurons distributed over an unexpectedly broad portion of the rostral two-thirds of the cerebral cortex converge to C7. This even included cortical areas controlling the hindlimbs (the fourth lumbar segment, L4). With aging, cell densities greatly declined, mainly due to axon branch elimination. Whole-cell recordings from spinal cord cells upon selective optogenetic stimulation of CS axons, and labeling of axons (DsRed) and presynaptic structures (synaptophysin) through cotransfection using exo utero electroporation, showed that overgrowing CS axons make synaptic connections with spinal cells in juveniles. This suggests that neuronal circuits involved in the CS tract to C7 are largely reorganized during development. By contrast, the cortical areas innervating L4 are limited to the conventional hindlimb area, and the cell distribution and density do not change during development. These findings call for an update of the traditional notion of somatotopic CS projection and imply that there are substantial developmental differences in the cortical control of forelimb and hindlimb movements, at least in rodents.
authors.affiliation: Department of Physiology, Teikyo University School of Medicine, Tokyo 173-8605, Japan, and.
authors.forename: Tsutomu
authors.identifier: http://orcid.org/0000-0003-1400-5024
authors.initials: T
authors.lastname: Kamiyama
authors.affiliation: Department of Physiology, Teikyo University School of Medicine, Tokyo 173-8605, Japan, and.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kameda
authors.affiliation: Department of Physiology, Teikyo University School of Medicine, Tokyo 173-8605, Japan, and.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Murabe
authors.affiliation: Department of Physiology, Teikyo University School of Medicine, Tokyo 173-8605, Japan, and.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuda
authors.affiliation: Department of Physiology, Teikyo University School of Medicine, Tokyo 173-8605, Japan, and.
authors.forename: Noboru
authors.initials: N
authors.lastname: Yoshioka
authors.affiliation: Division of Genetic Therapeutics, Jichi Medical University, Tochigi 329-0498, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mizukami
authors.affiliation: Division of Genetic Therapeutics, Jichi Medical University, Tochigi 329-0498, Japan.
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
authors.affiliation: Department of Physiology, Teikyo University School of Medicine, Tokyo 173-8605, Japan, and msakurai@med.teikyo-u.ac.jp.
authors.forename: Masaki
authors.initials: M
authors.lastname: Sakurai
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology; D002452:Cell Count; D066193:Cervical Cord / Q000502:physiology*; D005552:Forelimb / Q000294:innervation; D006614:Hindlimb / Q000294:innervation; D008159:Lumbar Vertebrae; D051379:Mice; D009068:Movement / Q000502:physiology; D011712:Pyramidal Tracts / Q000254:growth & development* / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology*
keywords: channelrhodopsin2; corticospinal projection; development; synapse elimination; topography; transient synapse