Early electrophysiological abnormalities in lumbar motoneurons in a transgenic mouse model of amyotrophic lateral sclerosis

Authors

  • Cyril Bories,

    1. Laboratoire de Plasticité et Physio-Pathologie de la Motricité, UMR 6196 CNRS, Aix-Marseille Université, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France
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  • Julien Amendola,

    1. Laboratoire de Plasticité et Physio-Pathologie de la Motricité, UMR 6196 CNRS, Aix-Marseille Université, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France
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  • Boris Lamotte d'Incamps,

    1. Laboratoire de Neurophysique et Physiologie, UMR 8119, CNRS, Université René Descartes, Paris, France
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  • Jacques Durand

    1. Laboratoire de Plasticité et Physio-Pathologie de la Motricité, UMR 6196 CNRS, Aix-Marseille Université, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France
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Dr J. Durand, as above.
E-mail: durand@dpm.cnrs-mrs.fr

Abstract

Amyotrophic lateral sclerosis is a lethal, adult-onset disease characterized by progressive degeneration of motoneurons. Recent data have suggested that the disease could be linked to abnormal development of the motor nervous system. Therefore, we investigated the electrical properties of lumbar motoneurons in an in-vitro neonatal spinal cord preparation isolated from SOD1G85R mice, which is a transgenic model of amyotrophic lateral sclerosis. The study was performed on young animals at the beginning of their second week, between postnatal days 6 and 10. Measurements of resting membrane potential and action potential characteristics of motoneurons were similar in wild-type and SOD1G85R mice. However, the input resistance of motoneurons from transgenic mice was significantly lower than that of wild-type animals, whereas their membrane capacitance was increased, strongly suggesting larger SOD1G85R motoneurons. Furthermore, the slope of the frequency–intensity curve was steeper in motoneurons from wild-type pups. Interestingly, the input resistance as well as the slope of the frequency–intensity curves of other spinal neurons did not show such differences. Finally, the amplitude of dorsal root-evoked potentials following high-intensity stimulation was significantly smaller in SOD1G85R motoneurons. The superoxide dismutase 1 mutation thus induces specific alterations of the functional properties of motoneurons early in development.

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