The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Transformation of nonfunctional spinal circuits into functional states after the loss of brain input
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Dynamic Sensorimotor Interactions in Locomotion
Rossignol, S., Dubuc, R., & Gossard, J.-P. (2006) · Physiological Reviews · doi:10.1152/physrev.00028.2005 · Cited by 1,096
Learning-Induced LTP in Neocortex
Rioult-Pedotti, M.-S., Friedman, D. J., & Donoghue, J. P. (2000) · Science · doi:10.1126/science.290.5491.533 · Cited by 1,014
Biological Pattern Generation: The Cellular and Computational Logic of Networks in Motion
Grillner, S. E. (2006) · Neuron · doi:10.1016/j.neuron.2006.11.008 · Cited by 920
LOCOMOTOR CIRCUITS IN THE MAMMALIAN SPINAL CORD
Kiehn, O. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.112910 · Cited by 868
Evidence for a Spinal Central Pattern Generator in Humans a
Dimitrijevic, M. R., Gerasimenko, Y. P., & Pinter, M. M. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb09062.x · Cited by 800
Self-citationCourtine, G., Song, B., Roy, R. R., Zhong, H., Herrmann, J. E., Ao, Y., Qi, J., Edgerton, V. R., & Sofroniew, M. V. (2007) · Nature Medicine · doi:10.1038/nm1682 · Cited by 730
Self-citationHuman Lumbosacral Spinal Cord Interprets Loading During Stepping
Harkema, S. J., Hurley, S. L., Patel, U. K., Requejo, P. S., Dobkin, B. H., & Edgerton, V. R. (1997) · Journal of Neurophysiology · doi:10.1152/jn.1997.77.2.797 · Cited by 604
Self-citationConvergent force fields organized in the frog's spinal cord
Giszter, S. F., Mussa-Ivaldi, F. A., & Bizzi, E. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-02-00467.1993 · Cited by 541
Courtine, G., Bunge, M. B., Fawcett, J. W., Grossman, R. G., Kaas, J. H., Lemon, R., Maier, I. C., Martin, J. H., Nudo, R. J., Ramón‐Cueto, A., et al. (2007) · Nature Medicine · doi:10.1038/nm1595 · Cited by 392
Self-citationGenerating the walking gait: role of sensory feedback
Pearson, K. G. (2004) · Progress in brain research · doi:10.1016/s0079-6123(03)43012-4 · Cited by 358
Spinal Cord Stimulation Restores Locomotion in Animal Models of Parkinson's Disease
Fuentes, R., Petersson, P., Siesser, W. B., Caron, M. G., & Nicolelis, M. A. L. (2009) · Science · doi:10.1126/science.1164901 · Cited by 298
Hindlimb stepping movements in complete spinal rats induced by epidural spinal cord stimulation
Ichiyama, R. M., Gerasimenko, Y. P., Zhong, H., Roy, R. R., & Edgerton, V. R. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.04.049 · Cited by 248
Self-citationModular Control of Limb Movements during Human Locomotion
Ivanenko, Y. P., Cappellini, G., Dominici, N., Poppele, R. E., & Lacquaniti, F. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2644-07.2007 · Cited by 237
Rattay, F., Minassian, K., & Dimitrijevic, M. (2000) · Spinal Cord · doi:10.1038/sj.sc.3101039 · Cited by 226
Contribution of Cutaneous Inputs From the Hindpaw to the Control of Locomotion. I. Intact Cats
Bouyer, L. J., & Rossignol, S. (2003) · Journal of Neurophysiology · doi:10.1152/jn.00496.2003 · Cited by 216
Barrière, G., Leblond, H., Provencher, J., & Rossignol, S. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5692-07.2008 · Cited by 216
Use-Dependent Modulation of Inhibitory Capacity in the Feline Lumbar Spinal Cord
Tillakaratne, N. J. K., de Leon, R. D., Hoang, T. X., Roy, R. R., Edgerton, V. R., & Tobin, A. J. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-08-03130.2002 · Cited by 202
Self-citationLavrov, I. A., Gerasimenko, Y., Ichiyama, R. M., Courtine, G., Zhong, H., Roy, R. R., & Edgerton, V. R. (2006) · Journal of Neurophysiology · doi:10.1152/jn.00325.2006 · Cited by 198
Self-citationTresch, M. C., & Bizzi, E. (1999) · Experimental Brain Research · doi:10.1007/s002210050908 · Cited by 196
Carhart, M. R., He, J., Herman, R. M., D'Luzansky, S., & Willis, W. T. (2004) · IEEE Transactions on Neural Systems and Rehabilitation Engineering · doi:10.1109/tnsre.2003.822763 · Cited by 177
Liu, J., & Jordan, L. M. (2005) · Journal of Neurophysiology · doi:10.1152/jn.00136.2005 · Cited by 171
Maier, I. C., Ichiyama, R. M., Courtine, G., Schnell, L., Lavrov, I. A., Edgerton, V. R., & Schwab, M. E. (2009) · Brain · doi:10.1093/brain/awp085 · Cited by 171
Self-citationRetention of Hindlimb Stepping Ability in Adult Spinal Cats After the Cessation of Step Training
de Leon, R. D., Hodgson, J. A., Roy, R. R., & Edgerton, V. R. (1999) · Journal of Neurophysiology · doi:10.1152/jn.1999.81.1.85 · Cited by 167
Self-citationStep Training Reinforces Specific Spinal Locomotor Circuitry in Adult Spinal Rats
Ichiyama, R. M., Courtine, G., Gerasimenko, Y., Yang, G. J., van den Brand, R., Lavrov, I. A., Zhong, H., Roy, R. R., & Edgerton, V. R. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1881-08.2008 · Cited by 167
Self-citationContribution of Cutaneous Inputs From the Hindpaw to the Control of Locomotion. II. Spinal Cats
Bouyer, L. J., & Rossignol, S. (2003) · Journal of Neurophysiology · doi:10.1152/jn.00497.2003 · Cited by 167
Plasticity of interneuronal networks of the functionally isolated human spinal cord
Harkema, S. J. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.07.012 · Cited by 164
Locomotor‐like movements evoked by leg muscle vibration in humans
Gurfinkel, V. S., Levik, Y. S., Kazennikov, O. V., & Селионов, В. А. (1998) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1998.00179.x · Cited by 163
Spinal cord reflexes induced by epidural spinal cord stimulation in normal awake rats
Gerasimenko, Y., Lavrov, I. A., Courtine, G., Ichiyama, R. M., Dy, C. J., Zhong, H., Roy, R. R., & Edgerton, V. R. (2006) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2006.05.004 · Cited by 162
Self-citationFacilitation of Stepping with Epidural Stimulation in Spinal Rats: Role of Sensory Input
Lavrov, I. A., Courtine, G., Dy, C. J., van den Brand, R., Fong, A. J., Gerasimenko, Y. P., Zhong, H., Roy, R. R., & Edgerton, V. R. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1069-08.2008 · Cited by 159
Self-citationTuning of a Basic Coordination Pattern Constructs Straight-Ahead and Curved Walking in Humans
Courtine, G., & Schieppati, M. (2004) · Journal of Neurophysiology · doi:10.1152/jn.00817.2003 · Cited by 158
Self-citationGrillner, S., & Wallén, P. (2002) · Brain Research Reviews · doi:10.1016/s0165-0173(02)00193-5 · Cited by 157
Epidural Stimulation Induced Modulation of Spinal Locomotor Networks in Adult Spinal Rats
Lavrov, I. A., Dy, C. J., Fong, A. J., Gerasimenko, Y., Courtine, G., Zhong, H., Roy, R. R., & Edgerton, V. R. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0080-08.2008 · Cited by 156
Self-citationPetruska, J. C., Ichiyama, R. M., Jindrich, D. L., Crown, E. D., Tansey, K. E., Roy, R. R., Edgerton, V. R., & Mendell, L. M. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2302-06.2007 · Cited by 151
Self-citationEarly locomotor training with clonidine in spinal cats
Chau, C., Barbeau, H., & Rossignol, S. (1998) · Journal of Neurophysiology · doi:10.1152/jn.1998.79.1.392 · Cited by 142
Gerasimenko, Y., Ichiyama, R. M., Lavrov, I. A., Courtine, G., Cai, L. L., Zhong, H., Roy, R. R., & Edgerton, V. R. (2007) · Journal of Neurophysiology · doi:10.1152/jn.00836.2007 · Cited by 137
Self-citationSpinal cord stimulation-induced locomotion in the adult cat
Iwahara, T., Atsuta, Y., García‐Rill, E., & Skinner, R. D. (1992) · Brain Research Bulletin · doi:10.1016/0361-9230(92)90235-p · Cited by 134
Courtine, G., Roy, R. R., Raven, J., Hodgson, J. A., McKay, H. M., Yang, H. S., Zhong, H., Tuszynski, M. H., & Edgerton, V. R. (2005) · Brain · doi:10.1093/brain/awh604 · Cited by 132
Self-citationModularity of Motor Output Evoked By Intraspinal Microstimulation in Cats
Lemay, M. A., & Grill, W. M. (2004) · Journal of Neurophysiology · doi:10.1152/jn.00235.2003 · Cited by 130
OEG implantation and step training enhance hindlimb-stepping ability in adult spinal transected rats
Kubasak, M. D., Jindrich, D. L., Zhong, H., Takeoka, A., McFarland, K. C., Muñoz-Quiles, C., Roy, R. R., Edgerton, V. R., Ramón‐Cueto, A., & Phelps, P. E. (2007) · Brain · doi:10.1093/brain/awm267 · Cited by 123
Self-citationThe human spinal cord interprets velocity-dependent afferent input during stepping
Beres-Jones, J. A. (2004) · Brain · doi:10.1093/brain/awh252 · Cited by 123
Degradation of neuronal function following a spinal cord injury: mechanisms and countermeasures
Dietz, V. H. (2004) · Brain · doi:10.1093/brain/awh255 · Cited by 120
Antri, M., Mouffle, C., Orsal, D., & Barthe, J. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02916.x · Cited by 116
Step Training-Dependent Plasticity in Spinal Cutaneous Pathways
Côté, M., & Gossard, J. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1486-04.2004 · Cited by 110
Gaunt, R. A., Procházka, A., Mushahwar, V. K., Guevremont, L., & ELLAWAY, P. H. (2006) · Journal of Neurophysiology · doi:10.1152/jn.00061.2006 · Cited by 110
Landry, E. S., Lapointe, N. P., Rouillard, C., Lévesque, D., Hedlund, P. B., & Guertin, P. A. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04917.x · Cited by 105
Engesser‐Cesar, C., Ichiyama, R. M., Nefas, A. L., Hill, M. A., Edgerton, V. R., Cotman, C. W., & Anderson, A. J. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05469.x · Cited by 90
Self-citation5-HT Receptors and the Neuromodulatory Control of Spinal Cord Function
Hochman, S., Garraway, S. M., Machacek, D., & Shay, B. L. (2001) · Frontiers in neuroscience · doi:10.1201/9781420042641.ch3 · Cited by 87
Barthélemy, D., Leblond, H., & Rossignol, S. (2007) · Journal of Neurophysiology · doi:10.1152/jn.00818.2006 · Cited by 82
Barthélemy, D., Leblond, H., Provencher, J., & Rossignol, S. (2006) · Journal of Neurophysiology · doi:10.1152/jn.00203.2006 · Cited by 69
Guevremont, L., Renzi, C. G., Norton, J. A., Kowalczewski, J. A., Saigal, R., & Mushahwar, V. K. (2006) · IEEE Transactions on Neural Systems and Rehabilitation Engineering · doi:10.1109/tnsre.2006.881592 · Cited by 65
Rudomin, P. (2002) · Progress in brain research · doi:10.1016/s0079-6123(02)36033-3 · Cited by 11
Cited by
Sorted by citations
Harkema, S., Gerasimenko, Y., Hodes, J., Burdick, J., Angeli, C., Chen, Y., Ferreira, C., Willhite, A., Rejc, E., Grossman, R. G., et al. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60547-3 · Cited by 1,229
Self-citationElectronic dura mater for long-term multimodal neural interfaces
Minev, I. R., Musienko, P., Hirsch, A., Barraud, Q., Wenger, N., Moraud, E. M., Gandar, J., Capogrosso, M., Milekovic, T., Asboth, L., et al. (2015) · Science · doi:10.1126/science.1260318 · Cited by 1,082
Self-citationConfronting false discoveries in single-cell differential expression
Squair, J. W., Gautier, M., Kathe, C., Anderson, M. A., James, N. D., Hutson, T. H., Hudelle, R., Qaiser, T., Matson, K. J. E., Barraud, Q., et al. (2021) · doi:10.1101/2021.03.12.435024 · Cited by 1,086
Self-citationRestoring Voluntary Control of Locomotion after Paralyzing Spinal Cord Injury
van den Brand, R., Heutschi, J., Barraud, Q., DiGiovanna, J., Bartholdi, K., Huerlimann, M., Friedli, L., Vollenweider, I., Moraud, E. M., Duis, S., et al. (2012) · Science · doi:10.1126/science.1217416 · Cited by 767
Self-citationMaterials and technologies for soft implantable neuroprostheses
Lacour, S. P., Courtine, G., & Guck, J. (2016) · Nature Reviews Materials · doi:10.1038/natrevmats.2016.63 · Cited by 738
Self-citation
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
