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Trpm5 channels encode bistability of spinal motoneurons and ensure motor control of hindlimbs in mice

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  • Rémi Bos

    (Institut de Neurosciences de la Timone (UMR7289), Aix-Marseille Université and CNRS)

  • Benoît Drouillas

    (Institut de Neurosciences de la Timone (UMR7289), Aix-Marseille Université and CNRS)

  • Mouloud Bouhadfane

    (Institut de Neurosciences de la Timone (UMR7289), Aix-Marseille Université and CNRS)

  • Emilie Pecchi

    (Institut de Neurosciences de la Timone (UMR7289), Aix-Marseille Université and CNRS)

  • Virginie Trouplin

    (Institut de Neurosciences de la Timone (UMR7289), Aix-Marseille Université and CNRS)

  • Sergiy M. Korogod

    (National Academy of Sciences of Ukraine)

  • Frédéric Brocard

    (Institut de Neurosciences de la Timone (UMR7289), Aix-Marseille Université and CNRS)

Abstract

Bistable motoneurons of the spinal cord exhibit warmth-activated plateau potential driven by Na+ and triggered by a brief excitation. The thermoregulating molecular mechanisms of bistability and their role in motor functions remain unknown. Here, we identify thermosensitive Na+-permeable Trpm5 channels as the main molecular players for bistability in mouse motoneurons. Pharmacological, genetic or computational inhibition of Trpm5 occlude bistable-related properties (slow afterdepolarization, windup, plateau potentials) and reduce spinal locomotor outputs while central pattern generators for locomotion operate normally. At cellular level, Trpm5 is activated by a ryanodine-mediated Ca2+ release and turned off by Ca2+ reuptake through the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump. Mice in which Trpm5 is genetically silenced in most lumbar motoneurons develop hindlimb paresis and show difficulties in executing high-demanding locomotor tasks. Overall, by encoding bistability in motoneurons, Trpm5 appears indispensable for producing a postural tone in hindlimbs and amplifying the locomotor output.

Suggested Citation

  • Rémi Bos & Benoît Drouillas & Mouloud Bouhadfane & Emilie Pecchi & Virginie Trouplin & Sergiy M. Korogod & Frédéric Brocard, 2021. "Trpm5 channels encode bistability of spinal motoneurons and ensure motor control of hindlimbs in mice," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27113-x
    DOI: 10.1038/s41467-021-27113-x
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    References listed on IDEAS

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    1. Karel Talavera & Keiko Yasumatsu & Thomas Voets & Guy Droogmans & Noriatsu Shigemura & Yuzo Ninomiya & Robert F. Margolskee & Bernd Nilius, 2005. "Heat activation of TRPM5 underlies thermal sensitivity of sweet taste," Nature, Nature, vol. 438(7070), pages 1022-1025, December.
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