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Transformation of nonfunctional spinal circuits into functional states after the loss of brain input
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After complete spinal cord transections that removed all supraspinal inputs in adult rats, combinations of serotonergic agonists and epidural electrical stimulation were able to acutely transform spinal networks from nonfunctional to highly functional and adaptive states as early as 1 week after injury. Using kinematics, physiological and anatomical analyses, we found that these interventions could recruit specific populations of spinal circuits, refine their control via sensory input and functionally remodel these locomotor pathways when combined with training. The emergence of these new functional states enabled full weight-bearing treadmill locomotion in paralyzed rats that was almost indistinguishable from voluntary stepping. We propose that, in the absence of supraspinal input, spinal locomotion can emerge from a combination of central pattern-generating capability and the ability of these spinal circuits to use sensory afferent input to control stepping. These findings provide a strategy by which individuals with spinal cord injuries could regain substantial levels of motor control.
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“Whereas the neurons located in the lumbar spinal cord are not directly damaged by the injury, the depletion of essential supraspinal commands renders them nonfunctional4.”
From The neurons that restore walking after paralysis (2022) · cites this paper as [4]
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Metadata
- Authors
- Courtine, G., Gerasimenko, Y., van den Brand, R., Yew, A., Musienko, P., Zhong, H., Song, B., Ao, Y., Ichiyama, R. M., Lavrov, I., Roy, R. R., Sofroniew, M. V., & Edgerton, V. R.
- Affiliations
- University of Zurich (CH)
- University of California, Los Angeles (US)
- Corresponding author
- Courtine, Grégoire
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2009-09-20
- Volume
- 12
- Issue
- 10
- Pages
- 1333-1342
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC2828944
- OpenAlex
- W1987284219
- Cited by
- 706
- References
- 51
- Citations by year
- 2026: 21 · 2025: 30 · 2024: 31 · 2023: 21 · 2022: 53 · 2021: 51 · 2020: 45 · 2019: 41 · 2018: 43 · 2017: 49 · 2016: 45 · 2015: 51 · 2014: 47 · 2013: 47 · 2012: 47
- FWCI
- 30.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Dana Foundation
- Christopher and Dana Reeve Foundation
- National Institute of Neurological Disorders and Stroke (NS-16333, P01NS016333)
- National Institute of Biomedical Imaging and Bioengineering (R01EB007615)
- 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 injury, spinal locomotor circuits, central pattern generator, serotonergic agonists, epidural stimulation, treadmill training, locomotor recovery, spinal cord transection
- MeSH terms
- Analysis of Variance, Animals, Biomechanical Phenomena, Brain, Disease Models, Animal, Electric Stimulation, Electromyography, Female, Gait, Hindlimb, Locomotion, Motor Activity, Nerve Net, Neural Pathways, Neuronal Plasticity, Physical Conditioning, Animal, Quipazine, Reflex, Spinal Cord Injuries, Time Factors, Oncogene Proteins v-fos, Rats, Sprague-Dawley, Serotonin Receptor Agonists, 8-Hydroxy-2-(di-n-propylamino)tetralin, Muscle, Skeletal, Recovery of Function, Principal Component Analysis, Rats
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