Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS
Hyperexcitability has been suggested to contribute to motoneuron degeneration in amyotrophic lateral sclerosis (ALS). If this is so, and given that the physiological type of a motor unit determines the relative susceptibility of its motoneuron in ALS, then one would expect the most vulnerable motone...
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doaj-e84ef059e33a431c86730f1b886b6e3d2021-05-05T15:45:38ZengeLife Sciences Publications LtdeLife2050-084X2018-03-01710.7554/eLife.30955Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALSMaría de Lourdes Martínez-Silva0Rebecca D Imhoff-Manuel1Aarti Sharma2CJ Heckman3Neil A Shneider4https://orcid.org/0000-0002-3223-7366Francesco Roselli5Daniel Zytnicki6https://orcid.org/0000-0002-0431-9604Marin Manuel7https://orcid.org/0000-0002-5344-3572Centre de Neurophysique, Physiologie et Pathologie, CNRS, Université Paris Descartes, Paris, FranceCentre de Neurophysique, Physiologie et Pathologie, CNRS, Université Paris Descartes, Paris, FranceCenter for Motor Neuron Biology and Disease, Department of Neurology, Columbia University, New York, United StatesDepartment of Physiology, Northwestern University, Feinberg School of Medicine, Chicago, United States; Department of Physical Medicine and Rehabilitation, Northwestern University, Feinberg School of Medicine, Chicago, United States; Department of Physical Therapy and Human Movement Science, Northwestern University, Feinberg School of Medicine, Chicago, United StatesCenter for Motor Neuron Biology and Disease, Department of Neurology, Columbia University, New York, United StatesDepartment of Neurology, Ulm University, Ulm, GermanyCentre de Neurophysique, Physiologie et Pathologie, CNRS, Université Paris Descartes, Paris, FranceCentre de Neurophysique, Physiologie et Pathologie, CNRS, Université Paris Descartes, Paris, France; Department of Physiology, Northwestern University, Feinberg School of Medicine, Chicago, United StatesHyperexcitability has been suggested to contribute to motoneuron degeneration in amyotrophic lateral sclerosis (ALS). If this is so, and given that the physiological type of a motor unit determines the relative susceptibility of its motoneuron in ALS, then one would expect the most vulnerable motoneurons to display the strongest hyperexcitability prior to their degeneration, whereas the less vulnerable should display a moderate hyperexcitability, if any. We tested this hypothesis in vivo in two unrelated ALS mouse models by correlating the electrical properties of motoneurons with their physiological types, identified based on their motor unit contractile properties. We found that, far from being hyperexcitable, the most vulnerable motoneurons become unable to fire repetitively despite the fact that their neuromuscular junctions were still functional. Disease markers confirm that this loss of function is an early sign of degeneration. Our results indicate that intrinsic hyperexcitability is unlikely to be the cause of motoneuron degeneration.https://elifesciences.org/articles/30955electrophysiologyin vivo intracellular recordingsmotor neuronmotoneuronfiring properties |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
María de Lourdes Martínez-Silva Rebecca D Imhoff-Manuel Aarti Sharma CJ Heckman Neil A Shneider Francesco Roselli Daniel Zytnicki Marin Manuel |
spellingShingle |
María de Lourdes Martínez-Silva Rebecca D Imhoff-Manuel Aarti Sharma CJ Heckman Neil A Shneider Francesco Roselli Daniel Zytnicki Marin Manuel Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS eLife electrophysiology in vivo intracellular recordings motor neuron motoneuron firing properties |
author_facet |
María de Lourdes Martínez-Silva Rebecca D Imhoff-Manuel Aarti Sharma CJ Heckman Neil A Shneider Francesco Roselli Daniel Zytnicki Marin Manuel |
author_sort |
María de Lourdes Martínez-Silva |
title |
Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS |
title_short |
Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS |
title_full |
Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS |
title_fullStr |
Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS |
title_full_unstemmed |
Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS |
title_sort |
hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of als |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2018-03-01 |
description |
Hyperexcitability has been suggested to contribute to motoneuron degeneration in amyotrophic lateral sclerosis (ALS). If this is so, and given that the physiological type of a motor unit determines the relative susceptibility of its motoneuron in ALS, then one would expect the most vulnerable motoneurons to display the strongest hyperexcitability prior to their degeneration, whereas the less vulnerable should display a moderate hyperexcitability, if any. We tested this hypothesis in vivo in two unrelated ALS mouse models by correlating the electrical properties of motoneurons with their physiological types, identified based on their motor unit contractile properties. We found that, far from being hyperexcitable, the most vulnerable motoneurons become unable to fire repetitively despite the fact that their neuromuscular junctions were still functional. Disease markers confirm that this loss of function is an early sign of degeneration. Our results indicate that intrinsic hyperexcitability is unlikely to be the cause of motoneuron degeneration. |
topic |
electrophysiology in vivo intracellular recordings motor neuron motoneuron firing properties |
url |
https://elifesciences.org/articles/30955 |
work_keys_str_mv |
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