Cited by 706Spinal Cord Injury ResearchNerve injury and regenerationStroke Rehabilitation and Recovery

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Transformation of nonfunctional spinal circuits into functional states after the loss of brain input

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Courtine, Grégoire, Gerasimenko, Yury, van den Brand, Rubia, Yew, Aileen, Musienko, Pavel, Zhong, Hui, Song, Bingbing, Ao, Yan, Ichiyama, Ronaldo M, Lavrov, Igor, Roy, Roland R, Sofroniew, Michael V, Edgerton, V Reggie·2009·Nature Neuroscience

DOI 10.1038/nn.2401PMC PMC2828944

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Abstract

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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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: Courtine, Grégoire
Gerasimenko, Yury
Zhong, Hui
Ichiyama, Ronaldo M
Lavrov, Igor
Sofroniew, Michael V
Edgerton, V Reggie
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2009-09-20
Volume: 12
Issue: 10
Pages: 1333-1342
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/nn.2401
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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