Early intrinsic hyperexcitability does not contribute to motoneuron degeneration in amyotrophic lateral sclerosis.
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.
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Ethics
Animal experimentation: The experiments were performed in accordance with European directives (86/609/CEE and 2010-63-UE) and the French legislation. They were approved by Paris Descartes University ethics committee (Permit Number: CEEA34.BLDI.065.12.). All surgery was performed under sodium pentobarbital anesthesia, and every effort was made to minimize suffering.
Reviewing Editor
- Ole Kiehn, Karolinska Institute, Sweden
Publication history
- Received: July 17, 2014
- Accepted: October 13, 2014
- Accepted Manuscript published: October 14, 2014 (version 1)
- Version of Record published: November 11, 2014 (version 2)
- Version of Record updated: May 12, 2017 (version 3)
Copyright
© 2014, Leroy et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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