title: Intrinsic properties of lumbar motor neurones in the adult G127insTGGG superoxide dismutase-1 mutant mouse in vivo: evidence for increased persistent inward currents.
abstract: OBJECTIVE
  Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by a preferential loss of motor neurones. Previous publications using in vitro neonatal preparations suggest an increased excitability of motor neurones in various superoxide dismutase-1 (SOD1) mutant mice models of ALS which may contribute to excitotoxicity of the motor neurones.
  
  
  METHODS
  Using intracellular recording, we tested this hypothesis in vivo in the adult presymptomatic G127insTGGG (G127X) SOD1 mutant mouse model of ALS.
  
  
  RESULTS
  At resting membrane potentials the basic intrinsic properties of lumbar motor neurones in the adult presymptomatic G127X mutant are not significantly different from those of wild type. However, at more depolarized membrane potentials, motor neurones in the G127X SOD1 mutants can sustain higher frequency firing, showing less spike frequency adaption (SFA) and with persistent inward currents (PICs) being activated at lower firing frequencies and being more pronounced.
  
  
  CONCLUSIONS
  We demonstrated that, in vivo, at resting membrane potential, spinal motor neurones of the adult G127X mice do not show an increased excitability. However, when depolarized they show evidence of an increased PIC and less SFA which may contribute to excitotoxicity of these neurones as the disease progresses.
authors.affiliation: Department of Neuroscience and Pharmacology, Panum Institute, University of Copenhagen, Denmark. claire@sund.ku.dk
authors.forename: C F
authors.initials: CF
authors.lastname: Meehan
authors.forename: M
authors.initials: M
authors.lastname: Moldovan
authors.forename: S L
authors.initials: SL
authors.lastname: Marklund
authors.forename: K S
authors.initials: KS
authors.lastname: Graffmo
authors.forename: J B
authors.initials: JB
authors.lastname: Nielsen
authors.forename: H
authors.initials: H
authors.lastname: Hultborn
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008161:Lumbosacral Region; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D009410:Nerve Degeneration / Q000473:pathology; D013116:Spinal Cord / Q000166:cytology*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1