Time course of alterations in adult spinal motoneuron properties in the sod1(G93a) mouse model of als

Seoan Huh, Charles J. Heckman, Marin Manuel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Although amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease, motoneuron electrical properties are already altered during embryonic development. Motoneurons must therefore exhibit a re-markable capacity for homeostatic regulation to maintain a normal motor output for most of the life of the patient. In the present article, we demonstrate how maintaining homeostasis could come at a very high cost. We studied the excitability of spinal motoneurons from young adult SOD1(G93A) mice to end-stage. Initially, homeostasis is highly successful in maintaining their overall excitability. This initial success, however, is achieved by pushing some cells far above the normal range of passive and active conductances. As the disease progresses, both passive and active conductances shrink below normal values in the surviving cells. This shrinkage may thus promote survival, implying the previously large values contribute to degeneration. These results support the hypothesis that motoneuronal homeostasis may be “hypervigilant” in ALS and a source of accumulating stress.

Original languageEnglish (US)
Article numberENEURO.0378-20.2021
Pages (from-to)1-16
Number of pages16
JournaleNeuro
Volume8
Issue number2
DOIs
StatePublished - Mar 1 2021

Funding

This work was supported by National Institutes of Health National Institute of Neurological Disorders and Stroke Grants R01NS077863 and R01NS110953. S.H. was supported by the National Science Foundation Graduate Research Fellowship. Correspondence should be addressed to Marin Manuel at [email protected]. https://doi.org/10.1523/ENEURO.0378-20.2021 Copyright © 2021 Huh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

Keywords

  • ALS
  • Electrophysiology
  • Homeostasis
  • In vivo recording
  • Motor neuron
  • Spinal cord

ASJC Scopus subject areas

  • General Neuroscience

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