Altered postnatal maturation of electrical properties in spinal motoneurons in a mouse model of amyotrophic lateral sclerosis

J Physiol. 2011 May 1;589(Pt 9):2245-60. doi: 10.1113/jphysiol.2010.200659. Epub 2011 Feb 28.


Spinal motoneurons are highly vulnerable in amyotrophic lateral sclerosis (ALS).Previous research using a standard animal model, the mutant superoxide dismutase-1 (SOD1)mouse, has revealed deficits in many cellular properties throughout its lifespan. The electrical properties underlying motoneuron excitability are some of the earliest to change; starting at 1 week postnatal, persistent inward currents (PICs) mediated by Na+ are upregulated and electrical conductance, a measure of cell size, increases. However, during this period these properties and many others undergo large developmental changes which have not been fully analysed.Therefore, we undertook a systematic analysis of electrical properties in more than 100 normal and mutant SOD1 motoneurons from 0 to 12 days postnatal, the neonatal to juvenile period.We compared normal mice with the most severe SOD1 model, the G93A high-expressor line. We found that the Na+ PIC and the conductance increased during development. However, mutant SOD1 motoneurons showed much greater increases than normal motoneurons; the mean Na+PIC in SOD1 motoneurons was double that of wild-type motoneurons. Additionally, in mutant SOD1 motoneurons the PIC mediated by Ca2+ increased, spike width decreased and the time course of the after-spike after-hyperpolarization shortened. These changes were advances of the normal effects of maturation. Thus, our results show that the development of normal and mutant SOD1 motoneurons follows generally similar patterns, but that the rate of development is accelerated in the mutant SOD1 motoneurons. Statistical analysis of all measured properties indicates that approximately 55% of changes attributed to the G93A SOD1 mutation can be attributed to an increased rate of maturation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials
  • Aging
  • Amyotrophic Lateral Sclerosis / enzymology
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / physiopathology*
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Calcium / metabolism
  • Disease Models, Animal
  • Electric Conductivity
  • Genotype
  • Humans
  • Kinetics
  • Mice
  • Mice, Transgenic
  • Motor Neurons / enzymology*
  • Mutation
  • Patch-Clamp Techniques
  • Phenotype
  • Sodium / metabolism
  • Spinal Nerves / enzymology
  • Spinal Nerves / physiopathology*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*
  • Superoxide Dismutase-1


  • SOD1 protein, human
  • Sodium
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Calcium