4.8 Article

A functional map for diverse forelimb actions within brainstem circuitry

期刊

NATURE
卷 590, 期 7846, 页码 445-+

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NATURE RESEARCH
DOI: 10.1038/s41586-020-03080-z

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  1. European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Descent) [692617]
  2. Swiss National Science Foundation
  3. Kanton Basel-Stadt
  4. Novartis Research Foundation
  5. European Research Council (ERC) [692617] Funding Source: European Research Council (ERC)

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The brainstem plays a key role in controlling body movements, especially skilled forelimb movements. By studying latRM populations, researchers have found that neuronal tuning in this region can affect forelimb actions, with excitatory latRM neurons influencing recruitment of brainstem and spinal cord circuits in different ways. Additionally, optogenetic stimulation of projection-stratified latRM populations can elicit diverse forelimb movements.
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 known(1-5), efforts to understand the neuronal underpinnings of skilled forelimb movements have focused predominantly on supra-brainstem centres and the spinal cord(6-12). 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.

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