title: Regenerated synapses in lamprey spinal cord are sparse and small even after functional recovery from injury.
abstract: Despite the potential importance that synapse regeneration plays in restoring neuronal function after spinal cord injury (SCI), even the most basic questions about the morphology of regenerated synapses remain unanswered. Therefore, we set out to gain a better understanding of central synapse regeneration by examining the number, distribution, molecular composition, and ultrastructure of regenerated synapses under conditions in which behavioral recovery from SCI was robust. To do so, we used the giant reticulospinal (RS) neurons of lamprey spinal cord because they readily regenerate, are easily identifiable, and contain large synapses that serve as a classic model for vertebrate excitatory neurotransmission. Using a combination of light and electron microscopy, we found that regenerated giant RS synapses regained the basic structures and presynaptic organization observed at control giant RS synapses at a time when behavioral recovery was nearly complete. However, several obvious differences remained. Most strikingly, regenerated giant RS axons produced very few synapses. In addition, presynaptic sites within regenerated axons were less complex, had fewer vesicles, and had smaller active zones than normal. In contrast, the densities of presynapses and docked vesicles were nearly restored to control values. Thus, robust functional recovery from SCI can occur even when the structures of regenerated synapses are sparse and small, suggesting that functional recovery is due to a more complex set of compensatory changes throughout the spinal network.
authors.affiliation: Section of Molecular Cell and Developmental Biology; Institute for Cell and Molecular Biology, Institute for Neuroscience, University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Oliphint
authors.forename: Naila
authors.initials: N
authors.lastname: Alieva
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Foldes
authors.forename: Eric D
authors.initials: ED
authors.lastname: Tytell
authors.forename: Billy Y-B
authors.initials: BY
authors.lastname: Lau
authors.forename: Jenna S
authors.initials: JS
authors.lastname: Pariseau
authors.forename: Avis H
authors.initials: AH
authors.lastname: Cohen
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Morgan
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology / Q000648:ultrastructure; D001696:Biomechanical Phenomena; D017629:Gap Junctions; D007814:Larva; D009416:Nerve Regeneration; D009474:Neurons / Q000473:pathology* / Q000648:ultrastructure; D048428:Petromyzon; D017729:Presynaptic Terminals / Q000473:pathology / Q000648:ultrastructure; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology; D013550:Swimming / Q000502:physiology; D013569:Synapses / Q000473:pathology* / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000473:pathology / Q000648:ultrastructure; D013997:Time Factors