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Elife. 2018 Mar 27;7. pii: e30955. doi: 10.7554/eLife.30955.

Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS.

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Centre de Neurophysique, Physiologie et Pathologie, CNRS, Université Paris Descartes, Paris, France.
Center for Motor Neuron Biology and Disease, Department of Neurology, Columbia University, New York, United States.
Department 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 States.
Department of Neurology, Ulm University, Ulm, Germany.


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.


electrophysiology; firing properties; in vivo intracellular recordings; motoneuron; motor neuron; mouse; neuroscience

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