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Elife. 2014 Oct 14;3. pii: e04046. doi: 10.7554/eLife.04046.

Early intrinsic hyperexcitability does not contribute to motoneuron degeneration in amyotrophic lateral sclerosis.

Author information

1
Laboratory of Neurophysics and Physiology, UMR 8119, Paris Descartes University, Paris, France.

Abstract

In amyotrophic lateral sclerosis (ALS) the large motoneurons that innervate the fast-contracting muscle fibers (F-type motoneurons) are vulnerable and degenerate in adulthood. In contrast, the small motoneurons that innervate the slow-contracting fibers (S-type motoneurons) are resistant and do not degenerate. Intrinsic hyperexcitability of F-type motoneurons during early postnatal development has long been hypothesized to contribute to neural degeneration in the adult. Here, we performed a critical test of this hypothesis by recording from identified F- and S-type motoneurons in the superoxide dismutase-1 mutant G93A (mSOD1), a mouse model of ALS at a neonatal age when early pathophysiological changes are observed. Contrary to the standard hypothesis, excitability of F-type motoneurons was unchanged in the mutant mice. Surprisingly, the S-type motoneurons of mSDO1 mice did display intrinsic hyperexcitability (lower rheobase, hyperpolarized spiking threshold). As S-type motoneurons are resistant in ALS, we conclude that early intrinsic hyperexcitability does not contribute to motoneuron degeneration.

KEYWORDS:

ALS; hyperexcitability; motoneuron; mouse; neuroscience

PMID:
25313866
PMCID:
PMC4227046
DOI:
10.7554/eLife.04046
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare that no competing interests exist.

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