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Locomotor speed control circuits in the caudal brainstem

Nature volume 551, pages 373377 (16 November 2017) | Download Citation


Locomotion is a universal behaviour that provides animals with the ability to move between places. Classical experiments have used electrical microstimulation to identify brain regions that promote locomotion1,2,3,4,5, but the identity of neurons that act as key intermediaries between higher motor planning centres and executive circuits in the spinal cord has remained controversial6,7,8,9,10,11,12,13,14. Here we show that the mouse caudal brainstem encompasses functionally heterogeneous neuronal subpopulations that have differential effects on locomotion. These subpopulations are distinguishable by location, neurotransmitter identity and connectivity. Notably, glutamatergic neurons within the lateral paragigantocellular nucleus (LPGi), a small subregion in the caudal brainstem, are essential to support high-speed locomotion, and can positively tune locomotor speed through inputs from glutamatergic neurons of the upstream midbrain locomotor region. By contrast, glycinergic inhibitory neurons can induce different forms of behavioural arrest mapping onto distinct caudal brainstem regions. Anatomically, descending pathways of glutamatergic and glycinergic LPGi subpopulations communicate with distinct effector circuits in the spinal cord. Our results reveal that behaviourally opposing locomotor functions in the caudal brainstem were historically masked by the unexposed diversity of intermingled neuronal subpopulations. We demonstrate how specific brainstem neuron populations represent essential substrates to implement key parameters in the execution of motor programs.

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We are grateful to M. Sigrist, M. Mielich, M. Pinto, J. Alonso, C. Hartmann and M. Theodore for experimental help, P. Tovote for advice with optogenetic technologies, S. Valencia Garcia and E. Arteaga Bracho for advice on EMG recordings, E. Jankowska for advice on cat brainstem nomenclature, A. Karpova for sharing the rAAV2-retro capsid plasmid before publication, R. Thierry and J. Eglinger from the FMI imaging facility and N. Ehrenfeuchter from the Biozentrum imaging facility for help and advice with image acquisition and analysis, P. Argast and P. Buchmann from the FMI mechanical workshop for building devices for behavioural experiments, M. Stadler and D. Gaidatzis for help with statistical analysis, and P. Caroni for discussions and comments on the manuscript. All authors were supported by an ERC Advanced Grant, the Swiss National Science Foundation, Kanton Basel-Stadt and Novartis Research Foundation, and the Louis Jeantet Prize for Medicine. M.S.E. was also supported by an HFSP long-term postdoctoral fellowship, Synapsis Foundation Grant and NARSAD Young Investigator Grant by the Brain and Behavior Foundation.

Author information


  1. Biozentrum, Department of Cell Biology, University of Basel, 4056 Basel, Switzerland

    • Paolo Capelli
    • , Chiara Pivetta
    • , Maria Soledad Esposito
    •  & Silvia Arber
  2. Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland

    • Paolo Capelli
    • , Chiara Pivetta
    • , Maria Soledad Esposito
    •  & Silvia Arber


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All authors were involved in the design of experiments. P.C. together with C.P. carried out most experiments, acquired and analysed data. M.S.E. carried out experiments related to MLR and MLR–Mc interactions, was involved in EMG and kinematic experiments, acquired and analysed data. S.A. initiated the project, designed experiments, analysed data and wrote the manuscript. All authors discussed the experiments and commented on the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Silvia Arber.

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Extended data

Supplementary information

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  1. 1.

    Supplementary Information

    This file contains additional discussion to the work presented in this study. It also contains Supplementary Table 1 which shows detailed statistical tests and sample sizes used in this study described in the accompanying main and extended data figures.

  2. 2.

    Reporting Summary


  1. 1.

    Stimulation of excitatory neurons in the caudal brainstem

    Representative examples of video sequences showing the behavioral effects of mice in the open field arena upon laser application to LPGi-vGlut2, GiA-vGlut2, GiV-vGlut2, and Gi-vGlut2 neurons.

  2. 2.

    Stimulation of inhibitory LPGi neuron subpopulations

    Representative examples of video sequences showing the behavioral effects of mice in the open field arena upon laser application to LPGi-vGAT, LPGi-GlyT2 and LPGi-Gad65 neurons.

  3. 3.

    Stimulation of glycinergic GiA, GiV and Gi neuron subpopulations

    Representative examples of video sequences showing the behavioral effects of mice in the open field arena upon laser application to GiA-GlyT2, GiV-GlyT2 and Gi-vGAT neurons.

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