Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS

María de Lourdes Martínez-Silva, Rebecca D. Imhoff-Manuel, Aarti Sharma, C. J. Heckman, Neil A. Shneider, Francesco Roselli, Daniel Zytnicki, Marin Manuel

Research output: Contribution to journalArticlepeer-review

89 Scopus citations


Hyperexcitability has been suggested to contribute to motoneuron degeneration in amyotrophic lateral sclerosis (ALS). If this is so, and given that the physiological type of a motor unit determines the relative susceptibility of its motoneuron in ALS, then one would expect the most vulnerable motoneurons to display the strongest hyperexcitability prior to their degeneration, whereas the less vulnerable should display a moderate hyperexcitability, if any. We tested this hypothesis in vivo in two unrelated ALS mouse models by correlating the electrical properties of motoneurons with their physiological types, identified based on their motor unit contractile properties. We found that, far from being hyperexcitable, the most vulnerable motoneurons become unable to fire repetitively despite the fact that their neuromuscular junctions were still functional. Disease markers confirm that this loss of function is an early sign of degeneration. Our results indicate that intrinsic hyperexcitability is unlikely to be the cause of motoneuron degeneration.

Original languageEnglish (US)
Article numbere30955
StatePublished - Mar 27 2018


  • electrophysiology
  • firing properties
  • in vivo intracellular recordings
  • motoneuron
  • motor neuron
  • mouse
  • neuroscience

ASJC Scopus subject areas

  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
  • General Neuroscience


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