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Cortico–reticulo–spinal circuit reorganization enables functional recovery after severe spinal cord contusion
Open accessAbstract
Severe spinal cord contusions interrupt nearly all brain projections to lumbar circuits producing leg movement. Failure of these projections to reorganize leads to permanent paralysis. Here we modeled these injuries in rodents. A severe contusion abolished all motor cortex projections below injury. However, the motor cortex immediately regained adaptive control over the paralyzed legs during electrochemical neuromodulation of lumbar circuits. Glutamatergic reticulospinal neurons with residual projections below the injury relayed the cortical command downstream. Gravity-assisted rehabilitation enabled by the neuromodulation therapy reinforced these reticulospinal projections, rerouting cortical information through this pathway. This circuit reorganization mediated a motor cortex-dependent recovery of natural walking and swimming without requiring neuromodulation. Cortico-reticulo-spinal circuit reorganization may also improve recovery in humans.
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“We also know that reticulospinal neurons from the vGi mediate the volitional modulation of walking during EES28.”
From The neurons that restore walking after paralysis (2022) · cites this paper as [28]
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Stolbkov, Y. K., & Gerasimenko, Y. P. (2024) · Успехи физиологических наук · doi:10.31857/s0301179824030067
Massai, E., Bonizzato, M., de Jesus, I., Drainville, R., & Martinez, M. (2024) · eLife · doi:10.7554/elife.92940.2
Sandoval, A., & Chen, B. (2024) · Springer eBooks · doi:10.1007/978-3-031-68237-7_53
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Hou, L., & Lei, Y. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.13.632757
Metadata
- Authors
- Asboth, L., Friedli, L., Beauparlant, J., Martinez-Gonzalez, C., Anil, S., Rey, E., Baud, L., Pidpruzhnykova, G., Anderson, M. A., Shkorbatova, P., Batti, L., Pagès, S., Kreider, J., Schneider, B. L., Barraud, Q., & Courtine, G.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Pavlov Institute of Physiology of the Russian Academy of Sciences (RU)
- Wyss Center for Bio and Neuroengineering (CH)
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2018-03-19
- Volume
- 21
- Issue
- 4
- Pages
- 576-588
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2791494966
- Cited by
- 324
- References
- 56
- Citations by year
- 2026: 22 · 2025: 52 · 2024: 41 · 2023: 37 · 2022: 38 · 2021: 51 · 2020: 28 · 2019: 37 · 2018: 16
- FWCI
- 25.22
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- Kissei
- Topics
- Health Sciences › Medicine › Clinical Neurology › Spinal Cord Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
- Keywords
- spinal cord contusion, circuit reorganization, functional recovery, reticulospinal neurons, motor cortex, locomotor recovery, paralysis, spinal cord injury
- MeSH terms
- Channelrhodopsins, Animals, Brain, Vestibular Nucleus, Lateral, Disease Models, Animal, Female, Male, Mice, Inbred C57BL, Mice, Transgenic, Motor Cortex, Psychomotor Performance, Quipazine, Rats, Inbred Lew, Spinal Cord, Spinal Cord Injuries, Serotonin Receptor Agonists, 8-Hydroxy-2-(di-n-propylamino)tetralin, Thy-1 Antigens, Recovery of Function, Mice, Rats
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