Brain-wide analysis of the supraspinal connectome reveals anatomical correlates to functional recovery after spinal injury

  1. Zimei Wang
  2. Adam Romanski
  3. Vatsal Mehra
  4. Yunfang Wang
  5. Matthew Brannigan
  6. Benjamin C Campbell
  7. Gregory A Petsko
  8. Pantelis Tsoulfas  Is a corresponding author
  9. Murray G Blackmore  Is a corresponding author
  1. Marquette University, United States
  2. University of Miami, United States
  3. Cornell University, United States

Abstract

The supraspinal connectome is essential for normal behavior and homeostasis and consists of numerous sensory, motor, and autonomic projections from brain to spinal cord. Study of supraspinal control and its restoration after damage has focused mostly on a handful of major populations that carry motor commands, with only limited consideration of dozens more that provide autonomic or crucial motor modulation. Here we assemble an experimental workflow to rapidly profile the entire supraspinal mesoconnectome in adult mice and disseminate the output in a web-based resource. Optimized viral labeling, 3D imaging, and registration to a mouse digital neuroanatomical atlas assigned tens of thousands of supraspinal neurons to 69 identified regions. We demonstrate the ability of this approach to clarify essential points of topographic mapping between spinal levels, to measure population-specific sensitivity to spinal injury, and to test relationships between region-specific neuronal sparing and variability in functional recovery. This work will spur progress by broadening understanding of essential but understudied supraspinal populations.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file or on the associated website 3Dmousebrain.com. Source Data 1 contains complete numerical data from all animals and Source Data 2 contains the numerical data used to generate all figures .

Article and author information

Author details

  1. Zimei Wang

    Department of Biomedical Sciences, Marquette University, Milwaukee, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Adam Romanski

    Department of Biomedical Sciences, Marquette University, Milwaukee, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Vatsal Mehra

    Department of Biomedical Sciences, Marquette University, Milwaukee, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yunfang Wang

    Department of Neurological Surgery, University of Miami, Miami, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Matthew Brannigan

    Department of Biomedical Sciences, Marquette University, Milwaukee, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Benjamin C Campbell

    Helen and Robert Appel Alzheimer's Disease Research Institute, Cornell University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8041-5561
  7. Gregory A Petsko

    Helen and Robert Appel Alzheimer's Disease Research Institute, Cornell University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3668-3694
  8. Pantelis Tsoulfas

    Department of Neurological Surgery, University of Miami, Miami, United States
    For correspondence
    ptsoulfa@Med.miami.edu
    Competing interests
    The authors declare that no competing interests exist.
  9. Murray G Blackmore

    Department of Biomedical Sciences, Marquette University, Milwaukee, United States
    For correspondence
    murray.blackmore@marquette.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9345-6688

Funding

National Institutes of Health (R01NS083983)

  • Murray G Blackmore

The Bryon Riesch Paralysis Foundation

  • Murray G Blackmore

The Miami Project to Cure Paralysis

  • Pantelis Tsoulfas

The Buoniconti fund

  • Pantelis Tsoulfas

State of Florida Red Light Camera Fund

  • Pantelis Tsoulfas

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#4013) of Marquette University. All surgery was performed under ketamine / xylazine anesthesia, and every effort was made to minimize suffering.

Copyright

© 2022, Wang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Zimei Wang
  2. Adam Romanski
  3. Vatsal Mehra
  4. Yunfang Wang
  5. Matthew Brannigan
  6. Benjamin C Campbell
  7. Gregory A Petsko
  8. Pantelis Tsoulfas
  9. Murray G Blackmore
(2022)
Brain-wide analysis of the supraspinal connectome reveals anatomical correlates to functional recovery after spinal injury
eLife 11:e76254.
https://doi.org/10.7554/eLife.76254

Share this article

https://doi.org/10.7554/eLife.76254

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