title: 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.
authors.affiliation: Laboratory of Neurophysics and Physiology, UMR 8119, Paris Descartes University, Paris, France.
authors.forename: Félix
authors.initials: F
authors.lastname: Leroy
authors.affiliation: Laboratory of Neurophysics and Physiology, UMR 8119, Paris Descartes University, Paris, France.
authors.forename: Boris
authors.identifier: http://orcid.org/0000-0003-4221-7526
authors.initials: B
authors.lastname: Lamotte d'Incamps
authors.affiliation: Laboratory of Neurophysics and Physiology, UMR 8119, Paris Descartes University, Paris, France.
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Imhoff-Manuel
authors.affiliation: Laboratory of Neurophysics and Physiology, UMR 8119, Paris Descartes University, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zytnicki
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004268:DNA-Binding Proteins; D003712:Dendrites / Q000378:metabolism; D004195:Disease Models, Animal; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology* / Q000502:physiology; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; C493465:Slc17a7 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; C107914:estrogen receptor-related receptor beta; D013482:Superoxide Dismutase; D020780:Matrix Metalloproteinase 9
keywords: ALS; hyperexcitability; motoneuron; mouse; neuroscience