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.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
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.
Extended data figures
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.
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.
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.