Motor antagonism exposed by spatial segregation and timing of neurogenesis

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Walking is a key motor behaviour of limbed animals, executed by contraction of functionally antagonistic muscle groups during swing and stance phases. Nevertheless, neuronal circuits regulating the activation of antagonistic extensor–flexor muscles remain poorly understood. Here we use monosynaptically restricted trans-synaptic viruses to elucidate premotor anatomical substrates for extensor–flexor control in mice. We observe a medio-lateral spatial segregation between extensor and flexor premotor interneurons in the dorsal spinal cord. These premotor interneuron populations are derived from common progenitor domains, but segregate by timing of neurogenesis. We find that proprioceptive sensory feedback from the periphery is targeted to medial extensor premotor populations and is required for extensor-specific connectivity profiles during development. Our findings provide evidence for a discriminating anatomical basis of antagonistic circuits at the level of premotor interneurons, and point to synaptic input and developmental ontogeny as key factors in the establishment of circuits regulating motor behavioural dichotomy.

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Figure 1: Spatial segregation of extensor and flexor premotor interneurons.
Figure 2: Adductor and flexor premotor interneurons co-segregate.
Figure 3: Timing of neurogenesis separates extensor and flexor populations.
Figure 4: Dorsal extensor premotor interneurons reside in proprioceptive termination area.
Figure 5: Proprioceptors control connectivity of extensor premotor interneurons.


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We are grateful to M. Sigrist for the generation of Taulox-stop-lox-SynGFP mice, M. Mielich for help in the production of viruses, P. Schwarb, L. Gelman, A. Ponti and M. Stadler for help and advice with image acquisition and statistical analysis, and to P. Caroni, G. Courtine, T. Jessell, B. Roska and P. Scheiffele for discussions and comments on the manuscript. We thank E. Callaway and K. Conzelmann for advice on virus work, and C. Birchmeier for Lbx1cre mice and Tlx3 antibodies. M.T. was supported by an EMBO long-term fellowship, M.T., A.E.S. and S.A. by an ERC Advanced Grant, the Swiss National Science Foundation, the Kanton Basel-Stadt, EU Framework Program 7 and the Novartis Research Foundation.

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M.T. carried out experiments and data acquisition, and was involved in design of experiments, data analysis and writing of the manuscript. A.E.S. developed the trans-synaptic virus method applied in this study. S.A. initiated the project and design of experiments, analysed data and wrote the manuscript. All authors discussed the experiments and commented on the manuscript.

Correspondence to Silvia Arber.

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Tripodi, M., Stepien, A. & Arber, S. Motor antagonism exposed by spatial segregation and timing of neurogenesis. Nature 479, 61–66 (2011) doi:10.1038/nature10538

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