title: Sparing of Descending Axons Rescues Interneuron Plasticity in the Lumbar Cord to Allow Adaptive Learning After Thoracic Spinal Cord Injury.
abstract: This study evaluated the role of spared axons on structural and behavioral neuroplasticity in the lumbar enlargement after a thoracic spinal cord injury (SCI). Previous work has demonstrated that recovery in the presence of spared axons after an incomplete lesion increases behavioral output after a subsequent complete spinal cord transection (TX). This suggests that spared axons direct adaptive changes in below-level neuronal networks of the lumbar cord. In response to spared fibers, we postulate that lumbar neuron networks support behavioral gains by preventing aberrant plasticity. As such, the present study measured histological and functional changes in the isolated lumbar cord after complete TX or incomplete contusion (SCI). To measure functional plasticity in the lumbar cord, we used an established instrumental learning paradigm (ILP). In this paradigm, neural circuits within isolated lumbar segments demonstrate learning by an increase in flexion duration that reduces exposure to a noxious leg shock. We employed this model using a proof-of-principle design to evaluate the role of sparing on lumbar learning and plasticity early (7 days) or late (42 days) after midthoracic SCI in a rodent model. Early after SCI or TX at 7 days, spinal learning was unattainable regardless of whether the animal recovered with or without axonal substrate. Failed learning occurred alongside measures of cell soma atrophy and aberrant dendritic spine expression within interneuron populations responsible for sensorimotor integration and learning. Alternatively, exposure of the lumbar cord to a small amount of spared axons for 6 weeks produced near-normal learning late after SCI. This coincided with greater cell soma volume and fewer aberrant dendritic spines on interneurons. Thus, an opportunity to influence activity-based learning in locomotor networks depends on spared axons limiting maladaptive plasticity. Together, this work identifies a time dependent interaction between spared axonal systems and adaptive plasticity in locomotor networks and highlights a critical window for activity-based rehabilitation.
authors.affiliation: School of Health and Rehabilitation Sciences, The Ohio State UniversityColumbus, OH, USA; Center for Brain and Spinal Cord Repair, The Ohio State UniversityColumbus, OH, USA.
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Hansen
authors.affiliation: School of Health and Rehabilitation Sciences, The Ohio State UniversityColumbus, OH, USA; Center for Brain and Spinal Cord Repair, The Ohio State UniversityColumbus, OH, USA; Neuroscience Graduate Program, The Ohio State UniversityColumbus, OH, USA.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Faw
authors.affiliation: School of Health and Rehabilitation Sciences, The Ohio State University Columbus, OH, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: White
authors.affiliation: School of Health and Rehabilitation Sciences, The Ohio State UniversityColumbus, OH, USA; Center for Brain and Spinal Cord Repair, The Ohio State UniversityColumbus, OH, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Buford
authors.affiliation: Department of Psychology, Texas A&M University College Station, TX, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Grau
authors.affiliation: School of Health and Rehabilitation Sciences, The Ohio State UniversityColumbus, OH, USA; Center for Brain and Spinal Cord Repair, The Ohio State UniversityColumbus, OH, USA.
authors.forename: D Michele
authors.initials: DM
authors.lastname: Basso
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003216:Conditioning, Operant / Q000502:physiology*; D049229:Dendritic Spines / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005781:Gelatin Sponge, Absorbable / Q000627:therapeutic use; D006490:Hemostatics / Q000627:therapeutic use; D007091:Image Processing, Computer-Assisted; D007395:Interneurons / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D059906:Neuroimaging; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D016622:Silver Staining; D013116:Spinal Cord / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D013997:Time Factors
chemical_list: D006490:Hemostatics
keywords: interneurons; learning; plasticity; recovery; sparing; spinal cord injury