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

Rémi Bos (), Benoît Drouillas, Mouloud Bouhadfane, Emilie Pecchi, Virginie Trouplin, Sergiy M. Korogod and Frédéric Brocard ()
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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

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-27113-x

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