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Spinal premotor interneurons controlling antagonistic muscles are spatially intermingled

View ORCID ProfileRemi Ronzano, View ORCID ProfileSophie Skarlatou, View ORCID ProfileBianca K. Barriga, View ORCID ProfileB. Anne Bannatyne, View ORCID ProfileGardave S. Bhumbra, View ORCID ProfileJoshua D. Foster, Jeffrey D. Moore, View ORCID ProfileCamille Lancelin, View ORCID ProfileAmanda Pocratsky, Mustafa Görkem Özyurt, View ORCID ProfileCalvin C. Smith, View ORCID ProfileAndrew J. Todd, David J. Maxwell, Andrew J. Murray, View ORCID ProfileSamuel L. Pfaff, View ORCID ProfileRobert M. Brownstone, View ORCID ProfileNiccolò Zampieri, View ORCID ProfileMarco Beato
doi: https://doi.org/10.1101/2021.02.10.430608
Remi Ronzano
1Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK
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  • ORCID record for Remi Ronzano
Sophie Skarlatou
2Max Delbrück Center for Molecular Medicine (MDC), Roybert-Rössle-Str. 10, 13092 Berlin, Germany
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  • ORCID record for Sophie Skarlatou
Bianca K. Barriga
6The Salk Institute for Biological Studies, Gene Expression Laboratory, 10010 North Torrey Pines Road, La Jolla CA 92037, USA
7Biological Sciences Graduate Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92037, USA
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B. Anne Bannatyne
3Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, West Medical Building, Glasgow G12 8QQ, UK
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Gardave S. Bhumbra
4Department of Neuroscience Physiology and Pharmacology (NPP), Gower Street, University College London, WC1E 6BT, UK
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Joshua D. Foster
4Department of Neuroscience Physiology and Pharmacology (NPP), Gower Street, University College London, WC1E 6BT, UK
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Jeffrey D. Moore
8Howard Hughes Medical Institute and Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, MA 02138, USA
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Camille Lancelin
1Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK
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Amanda Pocratsky
1Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK
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Mustafa Görkem Özyurt
1Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK
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Calvin C. Smith
1Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK
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  • ORCID record for Calvin C. Smith
Andrew J. Todd
3Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, West Medical Building, Glasgow G12 8QQ, UK
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David J. Maxwell
3Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, West Medical Building, Glasgow G12 8QQ, UK
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Andrew J. Murray
5Sainsbury Wellcome Centre for Neural Circuits and Behaviour, University College London, London W1T 4JG, UK
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Samuel L. Pfaff
6The Salk Institute for Biological Studies, Gene Expression Laboratory, 10010 North Torrey Pines Road, La Jolla CA 92037, USA
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  • For correspondence: zampieri@mdc-berlin.de pfaff@salk.edu r.brownstone@ucl.ac.uk m.beato@ucl.ac.uk
Robert M. Brownstone
1Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK
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  • For correspondence: zampieri@mdc-berlin.de pfaff@salk.edu r.brownstone@ucl.ac.uk m.beato@ucl.ac.uk
Niccolò Zampieri
2Max Delbrück Center for Molecular Medicine (MDC), Roybert-Rössle-Str. 10, 13092 Berlin, Germany
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  • For correspondence: zampieri@mdc-berlin.de pfaff@salk.edu r.brownstone@ucl.ac.uk m.beato@ucl.ac.uk
Marco Beato
4Department of Neuroscience Physiology and Pharmacology (NPP), Gower Street, University College London, WC1E 6BT, UK
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  • ORCID record for Marco Beato
  • For correspondence: zampieri@mdc-berlin.de pfaff@salk.edu r.brownstone@ucl.ac.uk m.beato@ucl.ac.uk
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Abstract

Elaborate behaviours are produced by tightly controlled flexor-extensor motor neuron activation patterns. Motor neurons are regulated by a network of interneurons within the spinal cord, but the computational processes involved in motor control are not fully understood. The neuroanatomical arrangement of motor and premotor neurons into topographic patterns related to their controlled muscles is thought to facilitate how information is processed by spinal circuits. Rabies retrograde monosynaptic tracing has been used to label premotor interneurons innervating specific motor neuron pools, with previous studies reporting topographic mediolateral positional biases in flexor and extensor premotor interneurons. To more precisely define how premotor interneurons contacting specific motor pools are organized we used multiple complementary viral-tracing approaches to minimize systematic biases associated with each method. Contrary to expectations, we found that premotor interneurons contacting motor pools controlling flexion and extension of the ankle are highly intermingled rather than segregated into specific domains like motor neurons. Thus, premotor spinal neurons controlling different muscles process motor instructions in the absence of clear spatial patterns among the flexor-extensor circuit components.

The paper can be downloaded in executable format as a MATLAB live script from https://github.com/marcobeato/Spinal_premotor_interneurons_controlling_antagonistic_muscles_are_sp atially_intermingled, where all the data are available An R version of the executable paper is available at https://mybinder.org/v2/gh/rronzano/Spinal_premotor_interneurons_controlling_antagonistic_muscles_ar e_spatially_intermingled.git/HEAD?urlpath=rstudio

Competing Interest Statement

RMB and AM are co-founder of Sania Therapeutics, Inc and consults for Sania Rx Ltd. CS is employed by Sania Therapeutics. The company's work is unrelated to the content of this paper

Footnotes

  • ↵§ co-senior authors

  • Updated following reviewer's comments. The paper now contains links to executable versions in MATLAB and in R

  • https://github.com/marcobeato/Spinal_premotor_interneurons_controlling_antagonistic_muscles_are_spatially_intermingled

  • https://mybinder.org/v2/gh/rronzano/Spinal_premotor_interneurons_controlling_antagonistic_muscles_are_spatially_intermingled.git/HEAD?urlpath=rstudio

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 29, 2022.
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Spinal premotor interneurons controlling antagonistic muscles are spatially intermingled
Remi Ronzano, Sophie Skarlatou, Bianca K. Barriga, B. Anne Bannatyne, Gardave S. Bhumbra, Joshua D. Foster, Jeffrey D. Moore, Camille Lancelin, Amanda Pocratsky, Mustafa Görkem Özyurt, Calvin C. Smith, Andrew J. Todd, David J. Maxwell, Andrew J. Murray, Samuel L. Pfaff, Robert M. Brownstone, Niccolò Zampieri, Marco Beato
bioRxiv 2021.02.10.430608; doi: https://doi.org/10.1101/2021.02.10.430608
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Spinal premotor interneurons controlling antagonistic muscles are spatially intermingled
Remi Ronzano, Sophie Skarlatou, Bianca K. Barriga, B. Anne Bannatyne, Gardave S. Bhumbra, Joshua D. Foster, Jeffrey D. Moore, Camille Lancelin, Amanda Pocratsky, Mustafa Görkem Özyurt, Calvin C. Smith, Andrew J. Todd, David J. Maxwell, Andrew J. Murray, Samuel L. Pfaff, Robert M. Brownstone, Niccolò Zampieri, Marco Beato
bioRxiv 2021.02.10.430608; doi: https://doi.org/10.1101/2021.02.10.430608

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