4.8 Article

Functional diversity for body actions in the mesencephalic locomotor region

Journal

CELL
Volume 184, Issue 17, Pages 4564-+

Publisher

CELL PRESS
DOI: 10.1016/j.cell.2021.07.002

Keywords

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Funding

  1. Portuguese Foundation for Science and Technology [PD/BD/105867/2014]
  2. Biozentrum PhD fellowship
  3. Synapsis Foundation
  4. Brain and Behavior Foundation NARSAD Young Investigator Grant
  5. HFSP Career Development Award
  6. CONICET
  7. PICT [2018-00607]
  8. European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Descent) [692617]
  9. Swiss National Science Foundation
  10. Kanton Basel-Stadt
  11. Novartis Research Foundation
  12. Louis Jeantet Prize for Medicine
  13. Fundação para a Ciência e a Tecnologia [PD/BD/105867/2014] Funding Source: FCT
  14. European Research Council (ERC) [692617] Funding Source: European Research Council (ERC)

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Research has shown the existence of functionally diverse neuronal populations in the mesencephalic locomotor region, with some controlling full-body behavior and others controlling forelimb behavior, stratified by projection target and exhibiting roles in action control beyond locomotion.
The mesencephalic locomotor region (MLR) is a key midbrain center with roles in locomotion. Despite extensive studies and clinical trials aimed at therapy-resistant Parkinson's disease (PD), debate on its function remains. Here, we reveal the existence of functionally diverse neuronal populations with distinct roles in control of body movements. We identify two spatially intermingled glutamatergic populations separable by axonal projections, mouse genetics, neuronal activity profiles, and motor functions. Most spinally projecting MLR neurons encoded the full-body behavior rearing. Loss- and gain-of-function optogenetic perturbation experiments establish a function for these neurons in controlling body extension. In contrast, Rbp4-transgenepositive MLR neurons project in an ascending direction to basal ganglia, preferentially encode the forelimb behaviors handling and grooming, and exhibit a role in modulating movement. Thus, the MLR contains glutamatergic neuronal subpopulations stratified by projection target exhibiting roles in action control not restricted to locomotion.

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