A functional map for diverse forelimb actions within brainstem circuitry

Ludwig Ruder, Riccardo Schina, Harsh Kanodia, Sara Valencia-Garcia, Chiara Pivetta and Silvia Arber ()
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Ludwig Ruder: University of Basel
Riccardo Schina: University of Basel
Harsh Kanodia: University of Basel
Sara Valencia-Garcia: University of Basel
Chiara Pivetta: University of Basel
Silvia Arber: University of Basel

Nature, 2021, vol. 590, issue 7846, 445-450

Abstract: Abstract The brainstem is a key centre in the control of body movements. Although the precise nature of brainstem cell types and circuits that are central to full-body locomotion are becoming known1–5, efforts to understand the neuronal underpinnings of skilled forelimb movements have focused predominantly on supra-brainstem centres and the spinal cord6–12. Here we define the logic of a functional map for skilled forelimb movements within the lateral rostral medulla (latRM) of the brainstem. Using in vivo electrophysiology in freely moving mice, we reveal a neuronal code with tuning of latRM populations to distinct forelimb actions. These include reaching and food handling, both of which are impaired by perturbation of excitatory latRM neurons. Through the combinatorial use of genetics and viral tracing, we demonstrate that excitatory latRM neurons segregate into distinct populations by axonal target, and act through the differential recruitment of intra-brainstem and spinal circuits. Investigating the behavioural potential of projection-stratified latRM populations, we find that the optogenetic stimulation of these populations can elicit diverse forelimb movements, with each behaviour stably expressed by individual mice. In summary, projection-stratified brainstem populations encode action phases and together serve as putative building blocks for regulating key features of complex forelimb movements, identifying substrates of the brainstem for skilled forelimb behaviours.

Date: 2021
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DOI: 10.1038/s41586-020-03080-z

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