title: Spinal cord maturation and locomotion in mice with an isolated cortex.
abstract: The spinal cord plays a key role in motor behavior. It relays major sensory information, receives afferents from supraspinal centers and integrates movement in the central pattern generators. Spinal motor output is controlled via corticofugal pathways including corticospinal and cortico-subcortical projections. Spinal cord injury damages descending supraspinal as well as ascending sensory pathways. In adult rodent models, plasticity of the spinal cord is thought to contribute to functional recovery. How much spinal cord function depends on cortical input is not well known. Here, we address this question using Celsr3/Foxg1 mice, in which cortico-subcortical connections (including corticospinal tract (CST) and the terminal sensory pathway, the thalamocortical tract) are genetically ablated during early development. Although Celsr3/Foxg1 mice are able to eat, walk, climb on grids and swim, open-field tests showed them to be hyperactive. When compared with normal littermates, mutant animals had reduced number of spinal motor neurons, with atrophic dendritic trees. Furthermore, motor axon terminals were decreased in number, and this was confirmed by electromyography. The number of cholinergic, calbindin, and calretinin-positive interneurons was moderately increased in the mutant spinal cord, whereas that of reelin and parvalbumin-positive interneurons was unchanged. As far as we know, our study provides the first genetic evidence that the spinal motor network does not mature fully in the absence of corticofugal connections, and that some motor function is preserved despite congenital absence of the CST.
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, PR China.
authors.forename: Q
authors.initials: Q
authors.lastname: Han
authors.forename: J
authors.initials: J
authors.lastname: Feng
authors.forename: Y
authors.initials: Y
authors.lastname: Qu
authors.forename: Y
authors.initials: Y
authors.lastname: Ding
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.forename: K-F
authors.initials: KF
authors.lastname: So
authors.forename: W
authors.initials: W
authors.lastname: Wu
authors.forename: L
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D002452:Cell Count; D002540:Cerebral Cortex / Q000002:abnormalities*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D051858:Forkhead Transcription Factors / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D008124:Locomotion / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D009046:Motor Neurons / Q000473:pathology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D009412:Nerve Fibers / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics; D011712:Pyramidal Tracts / Q000473:pathology / Q000503:physiopathology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D000091042:Reelin Protein; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology*
chemical_list: C117380:Celsr1 protein, mouse; D051858:Forkhead Transcription Factors; C489565:Foxg1 protein, mouse; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled; D000091042:Reelin Protein; C000717128:Reln protein, mouse
keywords: 5-HT; ALS; CB; CR; CST; Celsr3; ChAT; DH; EMG; GFAP; NF200; NMJ; PKCγ; PV; Protein Kinase C gamma; RST; ReST; Reln; SCI; TH; amyotrophic lateral sclerosis; calbindin; calretinin; choline acetyl transferase; corticospinal tract; dorsal horn; electromyogram; genetic animal model; glial fibrillary acidic protein; neural plasticity; neurofilament 200; neuromuscular junction; parvalbumin; reelin; reticulospinal tract; rubrospinal tract; serotonin; spinal cord injuries; spinal cord injury; tyrosine hydroxylase