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

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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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Felix Leroy

Paris Descartes University, Paris, France

For correspondence
felxfel@aol.com

Competing interests
The authors declare that no competing interests exist.
Boris Lamotte d'Incamps

Paris Descartes University, Paris, France

Competing interests
The authors declare that no competing interests exist.
Rebecca D Imhoff-Manuel

Paris Descartes University, Paris, France

Competing interests
The authors declare that no competing interests exist.
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.

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