title: Bridging the gap: a reticulo-propriospinal detour bypassing an incomplete spinal cord injury.
abstract: Anatomically incomplete spinal cord injuries are often followed by considerable functional recovery in patients and animal models, largely because of processes of neuronal plasticity. In contrast to the corticospinal system, where sprouting of fibers and rearrangements of circuits in response to lesions have been well studied, structural adaptations within descending brainstem pathways and intraspinal networks are poorly investigated, despite the recognized physiological significance of these systems across species. In the present study, spontaneous neuroanatomical plasticity of severed bulbospinal systems and propriospinal neurons was investigated following unilateral C4 spinal hemisection in adult rats. Injection of retrograde tracer into the ipsilesional segments C3-C4 revealed a specific increase in the projection from the ipsilesional gigantocellular reticular nucleus in response to the injury. Substantial regenerative fiber sprouting of reticulospinal axons above the injury site was demonstrated by anterograde tracing. Regrowing reticulospinal fibers exhibited excitatory, vGLUT2-positive varicosities, indicating their synaptic integration into spinal networks. Reticulospinal fibers formed close appositions onto descending, double-midline crossing C3-C4 propriospinal neurons, which crossed the lesion site in the intact half of the spinal cord and recrossed to the denervated cervical hemicord below the injury. These propriospinal projections around the lesion were significantly enhanced after injury. Our results suggest that severed reticulospinal fibers, which are part of the phylogenetically oldest motor command system, spontaneously arborize and form contacts onto a plastic propriospinal relay, thereby bypassing the lesion. These rearrangements were accompanied by substantial locomotor recovery, implying a potential physiological relevance of the detour in restoration of motor function after spinal injury.
authors.affiliation: Brain Research Institute, University of Zurich and Department of Health Sciences and Technology, ETH Zurich, 8057 Zurich, Switzerland, and linardfilli@hotmail.com linard.filli@usz.ch.
authors.forename: Linard
authors.identifier: http://orcid.org/0000-0003-3882-2504
authors.initials: L
authors.lastname: Filli
authors.affiliation: Brain Research Institute, University of Zurich and Department of Health Sciences and Technology, ETH Zurich, 8057 Zurich, Switzerland, and.
authors.forename: Anne Katrin
authors.initials: AK
authors.lastname: Engmann
authors.affiliation: Brain Research Institute, University of Zurich and Department of Health Sciences and Technology, ETH Zurich, 8057 Zurich, Switzerland, and.
authors.forename: Björn
authors.initials: B
authors.lastname: Zörner
authors.affiliation: Brain Research Institute, University of Zurich and Department of Health Sciences and Technology, ETH Zurich, 8057 Zurich, Switzerland, and.
authors.forename: Oliver
authors.initials: O
authors.lastname: Weinmann
authors.affiliation: Institute of Neuroinformatics, University and ETH Zurich, 8057 Zurich, Switzerland.
authors.forename: Timoleon
authors.initials: T
authors.lastname: Moraitis
authors.affiliation: Brain Research Institute, University of Zurich and Department of Health Sciences and Technology, ETH Zurich, 8057 Zurich, Switzerland, and.
authors.forename: Miriam
authors.initials: M
authors.lastname: Gullo
authors.affiliation: Brain Research Institute, University of Zurich and Department of Health Sciences and Technology, ETH Zurich, 8057 Zurich, Switzerland, and.
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Kasper
authors.affiliation: Brain Research Institute, University of Zurich and Department of Health Sciences and Technology, ETH Zurich, 8057 Zurich, Switzerland, and.
authors.forename: Regula
authors.initials: R
authors.lastname: Schneider
authors.affiliation: Brain Research Institute, University of Zurich and Department of Health Sciences and Technology, ETH Zurich, 8057 Zurich, Switzerland, and.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Schwab
mesh_terms: D000818:Animals; D001369:Axons; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism; D008526:Medulla Oblongata / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function; D012154:Reticular Formation / Q000378:metabolism / Q000473:pathology*; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: D050485:GABA Plasma Membrane Transport Proteins; C493475:Slc17a6 protein, rat; C493466:Slc17a7 protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2
keywords: locomotion; neuroanatomical plasticity; propriospinal; reticulospinal; spinal cord injury