title: Spinal cord injury induces serotonin supersensitivity without increasing intrinsic excitability of mouse V2a interneurons.
abstract: Denervation-induced plastic changes impair locomotor recovery after spinal cord injury (SCI). Spinal motoneurons become hyperexcitable after SCI, but the plastic responses of locomotor network interneurons (INs) after SCI have not been studied. Using an adult mouse SCI model, we analyzed the effects of complete spinal cord lesions on the intrinsic electrophysiological properties, excitability, and neuromodulatory responses to serotonin (5-HT) in mouse lumbar V2a spinal INs, which help regulate left-right alternation during locomotion. Four weeks after SCI, V2a INs showed almost no changes in baseline excitability or action potential properties; the only parameter that changed was a reduced input resistance. However, V2a INs became 100- to 1000-fold more sensitive to 5-HT. Immunocytochemical analysis showed that SCI caused a coordinated loss of serotonergic fibers and the 5-HT transporter (SERT). Blocking the SERT with citalopram in intact mice did not increase 5-HT sensitivity to the level seen after SCI. SCI also evoked an increase in 5-HT(2C) receptor cluster number and intensity, suggesting that several plastic changes cooperate in increasing 5-HT sensitivity. Our results suggest that different components of the spinal neuronal network responsible for coordinating locomotion are differentially affected by SCI, and highlight the importance of understanding these changes when considering therapies targeted at functional recovery.
authors.affiliation: Department of Neurobiology and Behavior, Seeley Mudd Hall, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Husch
authors.forename: Gabrielle N
authors.initials: GN
authors.lastname: Van Patten
authors.forename: Diana N
authors.initials: DN
authors.lastname: Hong
authors.forename: Moira M
authors.initials: MM
authors.lastname: Scaperotti
authors.forename: Nathan
authors.initials: N
authors.lastname: Cramer
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Harris-Warrick
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena / Q000187:drug effects*; D015283:Citalopram / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D018709:Statistics, Nonparametric; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics
chemical_list: D015283:Citalopram; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D044405:Receptor, Serotonin, 5-HT2C; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014157:Transcription Factors; C088975:Vsx2 protein, mouse; C485184:enhanced green fluorescent protein