Brain-wide analysis of the supraspinal connectome reveals anatomical correlates to functional recovery after spinal injury
- Marquette University, United States
- University of Miami, United States
- 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
Benjamin C Campbell
Murray G Blackmore
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.
Reviewing Editor
- Muriel Thoby-Brisson, CNRS Université de Bordeaux, France
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.
Version history
- Preprint posted: June 11, 2021 (view preprint)
- Received: December 9, 2021
- Accepted: July 12, 2022
- Accepted Manuscript published: July 15, 2022 (version 1)
- Version of Record published: August 2, 2022 (version 2)
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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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
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