Wireless closed-loop optogenetics across the entire dorsoventral spinal cord in mice
Open accessAbstract
Optoelectronic systems can exert precise control over targeted neurons and pathways throughout the brain in untethered animals, but similar technologies for the spinal cord are not well established. In the present study, we describe a system for ultrafast, wireless, closed-loop manipulation of targeted neurons and pathways across the entire dorsoventral spinal cord in untethered mice. We developed a soft stretchable carrier, integrating microscale light-emitting diodes (micro-LEDs), that conforms to the dura mater of the spinal cord. A coating of silicone-phosphor matrix over the micro-LEDs provides mechanical protection and light conversion for compatibility with a large library of opsins. A lightweight, head-mounted, wireless platform powers the micro-LEDs and performs low-latency, on-chip processing of sensed physiological signals to control photostimulation in a closed loop. We use the device to reveal the role of various neuronal subtypes, sensory pathways and supraspinal projections in the control of locomotion in healthy and spinal-cord injured mice.
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
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?
The fabrication of the micro-LED array was based on a previously validated technological design40 that we adapted to incorporate electrodes to deliver EES.
“The fabrication of the micro-LED array was based on a previously validated technological design40 that we adapted to incorporate electrodes to deliver EES, as illustrated in Extended Data Fig. 15a.”
From The neurons that restore walking after paralysis (2022) · cites this paper as [40]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
DeepLabCut: markerless pose estimation of user-defined body parts with deep learning
Mathis, A., Mamidanna, P., Cury, K. M., Abe, T., Murthy, V. N., Mathis, M. W., & Bethge, M. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0209-y · Cited by 5,187 · see citing works
Independent optical excitation of distinct neural populations
Klapoetke, N. C., Murata, Y., Kim, S. S., Pulver, S. R., Birdsey-Benson, A., Cho, Y. K., Morimoto, T. K., Chuong, A. S., Carpenter, E. J., Tian, Z., et al. (2014) · Nature Methods · doi:10.1038/nmeth.2836 · Cited by 2,344 · see citing works
Deisseroth, K. A. (2010) · Nature Methods · doi:10.1038/nmeth.f.324 · Cited by 1,884 · see citing works
Optogenetics in neural systems
Yizhar, O., Fenno, L. E., Davidson, T. J., Mogri, M., & Deisseroth, K. (2011) · Neuron · doi:10.1016/j.neuron.2011.06.004 · Cited by 1,881 · see citing works
iDISCO: A Simple, Rapid Method to Immunolabel Large Tissue Samples for Volume Imaging
Renier, N., Wu, Z., Simon, D. J., Yang, J. H., Ariel, P., & Tessier‐Lavigne, M. (2014) · Cell · doi:10.1016/j.cell.2014.10.010 · Cited by 1,838 · see citing works
Roth, B. L. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.040 · Cited by 1,742 · see citing works
Optogenetics: 10 years of microbial opsins in neuroscience
Deisseroth, K. A. (2015) · Nature Neuroscience · doi:10.1038/nn.4091 · Cited by 1,286 · see citing works
Injectable, Cellular-Scale Optoelectronics with Applications for Wireless Optogenetics
Kim, T.-I., McCall, J. G., Jung, Y. H., Huang, X., Siuda, E. R., Li, Y., Song, J., Song, Y. M., Pao, H. A., Kim, R.-H., et al. (2013) · Science · doi:10.1126/science.1232437 · Cited by 1,174 · see citing works
Electronic 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 · see citing works
Self-citationLight in diagnosis, therapy and surgery
Yun, S. H., & Kwok, S. J. J. (2017) · Nature Biomedical Engineering · doi:10.1038/s41551-016-0008 · Cited by 806 · see citing works
Soft, stretchable, fully implantable miniaturized optoelectronic systems for wireless optogenetics
Park, S. I., Brenner, D. S., Shin, G., Morgan, C. D., Copits, B. A., Chung, H. U., Pullen, M. Y., Noh, K. N., Davidson, S., Oh, S. J., et al. (2015) · Nature Biotechnology · doi:10.1038/nbt.3415 · Cited by 794 · see citing works
Transformation of nonfunctional spinal circuits into functional states after the loss of brain input
Courtine, G., Gerasimenko, Y., van den Brand, R., Yew, A., Musienko, P., Zhong, H., Song, B., Ao, Y., Ichiyama, R. M., Lavrov, I., et al. (2009) · Nature Neuroscience · doi:10.1038/nn.2401 · Cited by 706 · see citing works
Self-citationYaroslavsky, A. N., Schulze, P. C., Yaroslavsky, I. V., Schober, R., Ulrich, F., & Schwarzmaier, H.-J. (2002) · Physics in Medicine and Biology · doi:10.1088/0031-9155/47/12/305 · Cited by 656 · see citing works
Wirelessly powered, fully internal optogenetics for brain, spinal and peripheral circuits in mice
Montgomery, K. L., Yeh, A. J., Ho, J. S., Tsao, V., Mohan Iyer, S., Grosenick, L., Ferenczi, E. A., Tanabe, Y., Deisseroth, K., Delp, S. L., et al. (2015) · Nature Methods · doi:10.1038/nmeth.3536 · Cited by 565 · see citing works
Noninvasive optical inhibition with a red-shifted microbial rhodopsin
Miri, M. L., Busskamp, V., Young, A., Ogawa, M., Ramanlal, S. B., Forest, C. R., Chow, B. Y., Han, X., Lin, Y., Roska, B., et al. (2014) · DSpace@MIT (Massachusetts Institute of Technology) · Cited by 554 · see citing works
A wireless closed-loop system for optogenetic peripheral neuromodulation
Mickle, A. D., Won, S. M., Noh, K. N., Yoon, J., Meacham, K. W., Xue, Y., McIlvried, L. A., Copits, B. A., Samineni, V. K., Crawford, K. E., et al. (2019) · Nature · doi:10.1038/s41586-018-0823-6 · Cited by 514 · see citing works
The Microbial Opsin Family of Optogenetic Tools
Zhang, F., Vierock, J., Yizhar, O., Fenno, L. E., Tsunoda, S. P., Kianianmomeni, A., Prigge, M., Berndt, A., Cushman, J. C., Polle, J. E. W., et al. (2011) · Cell · doi:10.1016/j.cell.2011.12.004 · Cited by 507 · see citing works
Wireless Optofluidic Systems for Programmable In Vivo Pharmacology and Optogenetics
Jeong, J., McCall, J. G., Shin, G., Zhang, Y., Al‐Hasani, R., Kim, M. K., Li, S., Sim, J. Y., Jang, K., Shi, Y., et al. (2015) · Cell · doi:10.1016/j.cell.2015.06.058 · Cited by 493 · see citing works
Thermal constraints on in vivo optogenetic manipulations
Owen, S. F., Liu, M. H., & Kreitzer, A. C. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0422-3 · Cited by 406 · see citing works
Shin, G., Gomez, A. M., Al-Hasani, R., Jeong, Y. R., Kim, J., Xie, Z., Banks, A., Lee, S. M., Han, S. Y., Yoo, C. J., et al. (2017) · Neuron · doi:10.1016/j.neuron.2016.12.031 · Cited by 396 · see citing works
Wenger, N., Moraud, E. M., Gandar, J., Musienko, P., Capogrosso, M., Baud, L., Le Goff, C. G., Barraud, Q., Pavlova, N., Dominici, N., et al. (2016) · Nature Medicine · doi:10.1038/nm.4025 · Cited by 369 · see citing works
Self-citationThe mesoSPIM initiative: open-source light-sheet microscopes for imaging cleared tissue
Voigt, F. F., Kirschenbaum, D. S., Platonova, E., Pagès, S., Campbell, R. A. A., Kästli, R., Schaettin, M., Egolf, L., van der Bourg, A., Bethge, P., et al. (2019) · Nature Methods · doi:10.1038/s41592-019-0554-0 · Cited by 326 · see citing works
Asboth, L., Friedli, L., Beauparlant, J., Martinez-Gonzalez, C., Anil, S., Rey, E., Baud, L., Pidpruzhnykova, G., Anderson, M. A., Shkorbatova, P., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0093-5 · Cited by 324 · see citing works
Self-citationTakeoka, A., Vollenweider, I., Courtine, G., & Arber, S. (2014) · Cell · doi:10.1016/j.cell.2014.11.019 · Cited by 318 · see citing works
Self-citationEmerging Modalities and Implantable Technologies for Neuromodulation
Won, S. M., Song, E., Reeder, J. T., & Rogers, J. A. (2020) · Cell · doi:10.1016/j.cell.2020.02.054 · Cited by 293 · see citing works
In mice lacking V2a interneurons, gait depends on speed of locomotion
Crone, S. A., Zhong, G., Harris-Warrick, R., & Sharma, K. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.1206-09.2009 · Cited by 263 · see citing works
Flexible and stretchable nanowire-coated fibers for optoelectronic probing of spinal cord circuits
Lu, C., Park, S., Richner, T. J., Derry, A., Brown, I., Hou, C., Rao, S., Kang, J., Moritz, C. T., Fink, Y., et al. (2017) · Science Advances · doi:10.1126/sciadv.1600955 · Cited by 222 · see citing works
Paleolithic to Bronze Age Siberians Reveal Connections with First Americans and across Eurasia
He, Y. H., Spyrou, M. A., Karapetian, M. K., Shnaider, S. V., Radzevičiūtė, R., Nägele, K., Neumann, G. U., Penske, S., Zech, J., Lucas, M., et al. (2020) · Cell · doi:10.1016/j.cell.2020.04.037 · Cited by 218 · see citing works
Beyond the brain: Optogenetic control in the spinal cord and peripheral nervous system
Montgomery, K. L., Iyer, S. M., Christensen, A. J., Deisseroth, K., & Delp, S. L. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad7577 · Cited by 147 · see citing works
Takeoka, A., & Arber, S. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.03.010 · Cited by 129 · see citing works
Wireless optofluidic brain probes for chronic neuropharmacology and photostimulation
Qazi, R., Gomez, A. M., Castro, D. C., Zou, Z., Sim, J. Y., Xiong, Y., Abdo, J., Kim, C. Y., Anderson, A., Lohner, F., et al. (2019) · Nature Biomedical Engineering · doi:10.1038/s41551-019-0432-1 · Cited by 128 · see citing works
Configuration of electrical spinal cord stimulation through real-time processing of gait kinematics
Capogrosso, M., Wagner, F. B., Gandar, J., Moraud, E. M., Wenger, N., Milekovic, T., Shkorbatova, P. Y., Pavlova, N., Евгеньевич, М. П., Bézard, E., et al. (2018) · Nature Protocols · doi:10.1038/s41596-018-0030-9 · Cited by 123 · see citing works
Self-citationImplantable, wireless device platforms for neuroscience research
Gutruf, P., & Rogers, J. A. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.12.007 · Cited by 120 · see citing works
Fully implantable, battery-free wireless optoelectronic devices for spinal optogenetics
Samineni, V. K., Yoon, J., Crawford, K. E., Jeong, Y. R., McKenzie, K. C., Shin, G., Xie, Z., Sundaram, S. S., Li, Y., Yang, M. Y., et al. (2017) · Pain · doi:10.1097/j.pain.0000000000000968 · Cited by 119 · see citing works
A Multi-Sensor and Parallel Processing SoC for Miniaturized Medical Instrumentation
Schönle, P., Glaser, F., Burger, T., Rovere, G., Luca Benini, C., & Huang, Q. (2018) · IEEE Journal of Solid-State Circuits · doi:10.1109/jssc.2018.2815653 · Cited by 98 · see citing works
Self-citationAtlas of the Mouse Spinal Cord
WATSON, C. R. R., Paxinos, G., Kayalıoğlu, G., et al. (2009) · Elsevier eBooks · doi:10.1016/b978-0-12-374247-6.50020-1 · Cited by 96 · see citing works
Involvement of the corticospinal tract in the control of human gait
Barthélemy, D., Grey, M. J., Nielsen, J. B., & Bouyer, L. J. (2011) · Progress in brain research · doi:10.1016/b978-0-444-53355-5.00012-9 · Cited by 96 · see citing works
Epineural optogenetic activation of nociceptors initiates and amplifies inflammation
Michoud, F., Seehus, C. R., Schönle, P., Brun, N., Taub, D. G., Zhang, Z., Jain, A., Furfaro, I., Akouissi, O., Moon, R., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0673-2 · Cited by 91 · see citing works
Self-citationMignon, C., Tobin, D. J., Zeitouny, M., & Uzunbajakava, N. E. (2018) · Biomedical Optics Express · doi:10.1364/boe.9.000852 · Cited by 43 · see citing works
Wang, Y., Xie, K., Yue, H., Chen, X., Luo, X., Liao, Q., Liu, M., Wang, F., & Shi, P. (2020) · Nanoscale · doi:10.1039/c9nr07583f · Cited by 42 · see citing works
DTR‐mediated conditional cell ablation—Progress and challenges
Ruedl, C., & Jung, S. (2018) · European Journal of Immunology · doi:10.1002/eji.201847527 · Cited by 38 · see citing works
Locomotion: Circuits and Physiology
Kiehn, O., & Dougherty, K. J. (2012) · Springer eBooks · doi:10.1007/978-1-4614-1997-6_42 · Cited by 35 · see citing works
Noninvasive optical inhibition with a red-shifted microbial rhodopsin
Chuong, A. S., Miri, M. L., Busskamp, V., Matthews, G. A. C., Acker, L. C., Sørensen, A. T., Young, A., Klapoetke, N. C., Henninger, M. A., Kodandaramaiah, S. B., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3752 · Cited by 33 · see citing works
Defining Ecological Strategies in Neuroprosthetics
Courtine, G., & Bloch, J. (2015) · Neuron · doi:10.1016/j.neuron.2015.02.039 · Cited by 31 · see citing works
Self-citationOptogenetic spatial and temporal control of cortical circuits on a columnar scale
Roy, A., Osik, J. J., Ritter, N. J., Wang, S., Shaw, J. T., Fiser, J., & Hooser, S. D. V. (2015) · Journal of Neurophysiology · doi:10.1152/jn.00960.2015 · Cited by 29 · see citing works
Rostro-Caudal Inhibition of Hindlimb Movements in the Spinal Cord of Mice
Caggiano, V., Sur, M., & Bizzi, E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0100865 · Cited by 28 · see citing works
Optogenetic surface stimulation of the rat cervical spinal cord
Mondello, S. E., Sunshine, M. D., Fischedick, A. E., Dreyer, S. J., Horwitz, G. D., Anikeeva, P., Horner, P. J., & Moritz, C. T. (2018) · Journal of Neurophysiology · doi:10.1152/jn.00461.2017 · Cited by 20 · see citing works
Bieler, L., Grassner, L., Zaunmair, P., et al. (2018) · Heliyon · doi:10.1016/j.heliyon.2018.e00540 · Cited by 17 · see citing works
In-vitro study of control of human dura mater optical properties by acting of osmotical liquids
Bashkatov, A. N., Genina, E. A., Kochubey, V. I., et al. (2000) · Proceedings of SPIE, the International Society for Optical Engineering/Proceedings of SPIE · doi:10.1117/12.405939 · Cited by 9 · see citing works
Marx, V. (2014) · Nature Methods · doi:10.1038/nmeth.3221 · Cited by 3 · see citing works
Flagged first, then by citations
Research works printed but not linked: 6
- [18]Montgomery KL Iyer SM Christensen AJ Deisseroth K Delp SL Beyond the brain: Optogenetic control in the spinal cord and peripheral nervous system Science Translational Medicine 2016 10.1126/scitranslmedaad7577 27147590 · DOI
- [19]Mickle AD A wireless closed-loop system for optogenetic peripheral neuromodulation Nature 2019 10.1038/s41586-018-0823-6 PMC6336505 30602791 · DOI · Paper page
- [23]Shin G Flexible Near-Field Wireless Optoelectronics as Subdermal Implants for Broad Applications in Optogenetics Neuron 2017 10.1016/Jneuron.2016.12.031 PMC5377903 28132830 · DOI
- [24]Minev IR Electronic dura mater for long-term multimodal neural interfaces Science (80-) 2015 347 25574019
- [42]Takeoka A Vollenweider I Courtine G Arber S Muscle spindle feedback directs locomotor recovery and circuit reorganization after spinal cord injury Cell 2014 159 25525880
- [46]Asboth L Cortico-reticulo-spinal circuit reorganization enables functional recovery after severe spinal cord contusion Nature Neuroscience 2018 10.1038/s41593-018-0093-5 29556028 · DOI · Paper page
Cited by
Sorted by citations
The neurons that restore walking after paralysis
Kathe, C., Skinnider, M. A., Hutson, T. H., Regazzi, N., Gautier, M., Demesmaeker, R., Komi, S., Ceto, S., James, N. D., Cho, N., et al. (2022) · Nature · doi:10.1038/s41586-022-05385-7 · Cited by 304 · see citing works
Self-citation
- Authors
- Kathe, C., Michoud, F., Schönle, P., Rowald, A., Brun, N., Ravier, J., Furfaro, I., Paggi, V., Kim, K., Soloukey, S., Asboth, L., Hutson, T. H., Jelescu, I., Philippides, A., Alwahab, N., Gandar, J., Huber, D., De Zeeuw, C. I., Barraud, Q., Huang, Q., Lacour, S. P., & Courtine, G.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- École Polytechnique Fédérale de Lausanne (CH)
- Integrated Systems Laboratory (CH)
- Erasmus MC (NL)
- Centre d'Imagerie BioMedicale (CH)
- University of Geneva (CH)
- Corresponding author
- Lacour, Stéphanie P.
- Courtine, Grégoire
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2021-09-27
- Volume
- 40
- Issue
- 2
- Pages
- 198-208
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC7612390
- OpenAlex
- W3201959246
- Cited by
- 119
- References
- 50
- Citations by year
- 2026: 15 · 2025: 26 · 2024: 32 · 2023: 23 · 2022: 21 · 2021: 2
- FWCI
- 8.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature Biotechnology (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion)
- PubMed Central (acceptedVersion)
- SERVAL (Université de Lausanne) (acceptedVersion)
- Archive ouverte UNIGE (University of Geneva) (acceptedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- IRIS (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (130850, 310030)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Keywords
- closed-loop optogenetics, spinal cord, micro-LEDs, opsin, locomotion control, spinal cord injury, sensory pathways
- MeSH terms
- Animals, Brain, Neurons, Spinal Cord, Mice, Wireless Technology, Optogenetics
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
