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

  1. Felix Leroy  Is a corresponding author
  2. Boris Lamotte d'Incamps
  3. Rebecca D Imhoff-Manuel
  4. Daniel Zytnicki
  1. Paris Descartes University, France
Research Article
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Cite this article as: eLife 2014;3:e04046 doi: 10.7554/eLife.04046

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.

Article and author information

Author details

  1. Felix Leroy

    Paris Descartes University, Paris, France
    For correspondence
    felxfel@aol.com
    Competing interests
    The authors declare that no competing interests exist.
  2. Boris Lamotte d'Incamps

    Paris Descartes University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Rebecca D Imhoff-Manuel

    Paris Descartes University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Daniel Zytnicki

    Paris Descartes University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

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

  1. Ole Kiehn, Karolinska Institute, Sweden

Publication history

  1. Received: July 17, 2014
  2. Accepted: October 13, 2014
  3. Accepted Manuscript published: October 14, 2014 (version 1)
  4. Version of Record published: November 11, 2014 (version 2)
  5. 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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