Optical control of neuronal excitation and inhibition using a single opsin protein, ChR2
Open accessAbstract
The effect of electrical stimulation on neuronal membrane potential is frequency dependent. Low frequency electrical stimulation can evoke action potentials, whereas high frequency stimulation can inhibit action potential transmission. Optical stimulation of channelrhodopsin-2 (ChR2) expressed in neuronal membranes can also excite action potentials. However, it is unknown whether optical stimulation of ChR2-expressing neurons produces a transition from excitation to inhibition with increasing light pulse frequencies. Here we report optical inhibition of motor neuron and muscle activity in vivo in the cooled sciatic nerves of Thy1-ChR2-EYFP mice. We also demonstrate all-optical single-wavelength control of neuronal excitation and inhibition without co-expression of inhibitory and excitatory opsins. This all-optical system is free from stimulation-induced electrical artifacts and thus provides a new approach to investigate mechanisms of high frequency inhibition in neuronal circuits in vivo and in vitro.
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?
A study with mice proved that both excitation and inhibition can be obtained through using only channelrhodopsin-2.
“A study done with mice proved that both excitation and inhibition can be obtained through using only channelrhodopsin-2 [133].”
From Interfaces with the peripheral nervous system for the control of a neuroprosthetic limb: a review (2020) · cites this paper as [133]
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
NIH Image to ImageJ: 25 years of image analysis
Schneider, C. A., Rasband, W. S., & Eliceiri, K. W. (2012) · Nature Methods · doi:10.1038/nmeth.2089 · Cited by 64,638 · see citing works
(1982) · Trends in Neurosciences · doi:10.1016/0166-2236(82)90076-5 · Cited by 9,148 · see citing works
Millisecond-timescale, genetically targeted optical control of neural activity
Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G., & Deisseroth, K. A. (2005) · Nature Neuroscience · doi:10.1038/nn1525 · Cited by 4,831 · see citing works
Self-citationThe development and application of optogenetics
Fenno, L., Yizhar, O., & Deisseroth, K. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113817 · Cited by 1,822 · see citing works
Self-citationOptical Deconstruction of Parkinsonian Neural Circuitry
Gradinaru, V., Mogri, M., Thompson, K. R., Henderson, J. M., & Deisseroth, K. A. (2009) · Science · doi:10.1126/science.1167093 · Cited by 1,536 · see citing works
Self-citationMolecular and Cellular Approaches for Diversifying and Extending Optogenetics
Gradinaru, V., Zhang, F., Ramakrishnan, C., Mattis, J., Prakash, R., Diester, I., Goshen, I., Thompson, K. R., & Deisseroth, K. A. (2010) · Cell · doi:10.1016/j.cell.2010.02.037 · Cited by 999 · see citing works
Self-citationMattis, J., Tye, K. M., Ferenczi, E. A., Ramakrishnan, C., O'Shea, D. J., Prakash, R., Gunaydin, L. A., Hyun, M., Fenno, L. E., Gradinaru, V., et al. (2012) · Nature Methods · doi:10.1038/nmeth.1808 · Cited by 780 · see citing works
Self-citationGunaydin, L. A., Yizhar, O., Berndt, A., Sohal, V. S., Deisseroth, K., & Hegemann, P. (2010) · Nature Neuroscience · doi:10.1038/nn.2495 · Cited by 757 · see citing works
Self-citationArenkiel, B. R., Peca, J., Davison, I. G., Feliciano, C., Deisseroth, K., Augustine, G. J., Ehlers, M. D., & Feng, G. (2007) · Neuron · doi:10.1016/j.neuron.2007.03.005 · Cited by 755 · see citing works
Self-citationLi, X., Gutierrez, D. V., Hanson, M. G., Han, J., Mark, M. D., Chiel, H. J., Hegemann, P., Landmesser, L. T., & Herlitze, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509030102 · Cited by 543 · see citing works
Cholinergic Interneurons Control Local Circuit Activity and Cocaine Conditioning
Witten, I. B., Lin, S.-C., Brodsky, M., Prakash, R., Diester, I., Anikeeva, P., Gradinaru, V., Ramakrishnan, C., & Deisseroth, K. (2010) · Science · doi:10.1126/science.1193771 · Cited by 467 · see citing works
Self-citationOptetrode: a multichannel readout for optogenetic control in freely moving mice
Anikeeva, P., Andalman, A. S., Witten, I. B., Warden, M. R., Goshen, I., Grosenick, L., Gunaydin, L. A., Frank, L. M., & Deisseroth, K. A. (2011) · Nature Neuroscience · doi:10.1038/nn.2992 · Cited by 381 · see citing works
Self-citationNerve conduction block utilising high-frequency alternating current
Kilgore, K. L., & Bhadra, N. (2004) · Medical & Biological Engineering & Computing · doi:10.1007/bf02344716 · Cited by 286 · see citing works
Peripheral Neurostimulation for Treatment of Intractable Occipital Neuralgia
Slavin, K. V., Nersesyan, H., & Wess, C. (2005) · Neurosurgery · doi:10.1227/01.neu.0000192163.55428.62 · Cited by 251 · see citing works
Bamann, C., Kirsch, T., Nagel, G., & Bamberg, E. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.10.072 · Cited by 249 · see citing works
Optical control of zebrafish behavior with halorhodopsin
Arrenberg, A. B., Bene, F. D., & Baier, H. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906252106 · Cited by 244 · see citing works
High‐frequency electrical conduction block of mammalian peripheral motor nerve
Bhadra, N., & Kilgore, K. L. (2005) · Muscle & Nerve · doi:10.1002/mus.20428 · Cited by 239 · see citing works
Orderly recruitment of motor units under optical control in vivo
Llewellyn, M. E., Thompson, K. R., Deisseroth, K., & Delp, S. L. (2010) · Nature Medicine · doi:10.1038/nm.2228 · Cited by 217 · see citing works
Self-citationSlavin, K. V., Colpan, M. E., Munawar, N., et al. (2006) · Neurosurgical FOCUS · doi:10.3171/foc.2006.21.6.8 · Cited by 200 · see citing works
Suppression of axonal conduction by sinusoidal stimulation in rat hippocampusin vitro
Jensen, A. L., & Durand, D. M. (2007) · Journal of Neural Engineering · doi:10.1088/1741-2560/4/2/001 · Cited by 180 · see citing works
Direct current electrical conduction block of peripheral nerve
Bhadra, N., & Kilgore, K. L. (2004) · IEEE Transactions on Neural Systems and Rehabilitation Engineering · doi:10.1109/tnsre.2004.834205 · Cited by 178 · see citing works
High frequency stimulation can block axonal conduction
Jensen, A. L., & Durand, D. M. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.07.023 · Cited by 176 · see citing works
Binding, J., Arous, J. B., Léger, J., Gigan, S., Boccara, C., & Bourdieu, L. (2011) · Optics Express · doi:10.1364/oe.19.004833 · Cited by 173 · see citing works
Reversible Blocking of Nerve Conduction by Alternating-Current Excitation
Tanner, J. A. (1962) · Nature · doi:10.1038/195712b0 · Cited by 159 · see citing works
Camilleri, M., Toouli, J., Herrera, M. F., Kulseng, B. E., Kow, L., Pantoja, J. P., Mårvik, R., Johnsen, G., Billington, C. J., Moody, F. G., et al. (2008) · Surgery · doi:10.1016/j.surg.2008.03.015 · Cited by 159 · see citing works
Simulation of high-frequency sinusoidal electrical block of mammalian myelinated axons
Bhadra, N., Lahowetz, E. A., Foldes, S. T., & Kilgore, K. L. (2007) · Journal of Computational Neuroscience · doi:10.1007/s10827-006-0015-5 · Cited by 144 · see citing works
Zhang, Y., Ivanova, E., Bi, A., & Pan, Z. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0184-09.2009 · Cited by 132 · see citing works
Inversion of the current-distance relationship by transient depolarization
Grill, W. M., & Mortimer, J. T. (1997) · IEEE Transactions on Biomedical Engineering · doi:10.1109/10.553708 · Cited by 109 · see citing works
Voltage‐ and time‐dependent properties of the recombinant rat vanilloid receptor (rVR1)
Gunthorpe, M. J., Harries, M. H., Prinjha, R. K., Davis, J. B., & Randall, A. D. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.t01-1-00747.x · Cited by 96 · see citing works
Localized Electrical Nerve Blocking
Williamson, R., & Andrews, B. J. (2005) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2004.842790 · Cited by 96 · see citing works
Mechanism of Nerve Conduction Block Induced by High-Frequency Biphasic Electrical Currents
Zhang, X., Roppolo, J. R., de Groat, W. C., & Tai, C. (2006) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2006.884640 · Cited by 93 · see citing works
Kleinlogel, S., Terpitz, U., Legrum, B., Gökbuget, D., Boyden, E. S., Bamann, C., Wood, P. G., & Bamberg, E. (2011) · Nature Methods · doi:10.1038/nmeth.1766 · Cited by 81 · see citing works
Effects of high-frequency alternating current on axonal conduction through the vagus nerve
Waataja, J. J., Tweden, K. S., & Honda, C. N. (2011) · Journal of Neural Engineering · doi:10.1088/1741-2560/8/5/056013 · Cited by 78 · see citing works
Differential blocking of myelinated nerve fibres by transient depolarization
Sassen, M., & Zimmermann, M. (1973) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00592788 · Cited by 67 · see citing works
Chronic nerve compression alters schwann cell myelin architecture in a murine model
Gupta, R., Nassiri, N., Hazel, A., Bathen, M., & Mozaffar, T. (2011) · Muscle & Nerve · doi:10.1002/mus.22276 · Cited by 58 · see citing works
Selective activation of C-fibers
Zimmermann, M. (1968) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00362643 · Cited by 56 · see citing works
Zhang, X., Roppolo, J. R., de Groat, W. C., & Tai, C. (2006) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2006.873689 · Cited by 41 · see citing works
Selective Activation of C-Fibers*
Zimmermann, D., & April, R. (1968) · Cited by 41 · see citing works
Optical inhibition of motor nerve and muscle activity in vivo
Liske, H., Towne, C. L., Anikeeva, P., Zhao, S., Feng, G., Deisseroth, K. A., & Delp, S. L. (2012) · Muscle & Nerve · doi:10.1002/mus.23696 · Cited by 38 · see citing works
Self-citationLiu, H., Roppolo, J. R., de Groat, W. C., & Tai, C. (2008) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2008.2006013 · Cited by 37 · see citing works
Analysis of nerve conduction block induced by direct current
Tai, C., Roppolo, J. R., & de Groat, W. C. (2009) · Journal of Computational Neuroscience · doi:10.1007/s10827-009-0137-7 · Cited by 36 · see citing works
Han, X. (2009) · Frontiers in Molecular Neuroscience · doi:10.3389/neuro.02.012.2009 · Cited by 32 · see citing works
High Frequency Mammalian Nerve Conduction Block: Simulations and Experiments
Kilgore, K. L., & Bhadra, N. (2006) · doi:10.1109/iembs.2006.259254 · Cited by 29 · see citing works
Wang, J., Shen, B. Q., Roppolo, J. R., et al. (2007) · Journal of Computational Neuroscience · doi:10.1007/s10827-007-0050-x · Cited by 25 · see citing works
Tai, C., Wang, J., Chancellor, M. B., et al. (2008) · The Journal of Urology · doi:10.1016/j.juro.2008.04.138 · Cited by 24 · see citing works
Voltage- and temperature-dependent gating of heterologously expressed channelrhodopsin-2
Chater, T. E., Henley, J. M., Brown, J. T., & Randall, A. D. (2010) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2010.07.033 · Cited by 23 · see citing works
Caldwell, J. H., Herin, G. A., Nagel, G., Bamberg, E., Scheschonka, A., & Betz, H. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802593200 · Cited by 22 · see citing works
Fast, repetitive light-activation of CaV3.2 using Channelrhodopsin 2
Prigge, M., Rösler, A., & Hegemann, P. (2010) · Channels · doi:10.4161/chan.4.3.11888 · Cited by 21 · see citing works
High-frequency limit of neural stimulation with ChR2
Grossman, N., Nikolić, K., Grubb, M. S., et al. (2011) · doi:10.1109/iembs.2011.6091034 · Cited by 18 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
A mm-Sized Wireless Implantable Device for Electrical Stimulation of Peripheral Nerves
Charthad, J., Chang, T. C., Liu, Z., Sawaby, A., Weber, M. J., Baker, S., Gore, F., Felt, S. A., & Arbabian, A. (2018) · IEEE Transactions on Biomedical Circuits and Systems · doi:10.1109/tbcas.2018.2799623 · Cited by 230 · 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
Self-citationA review for the peripheral nerve interface designer
Larson, C. E., & Meng, E. (2020) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2019.108523 · Cited by 133 · see citing works
Interfaces with the peripheral nervous system for the control of a neuroprosthetic limb: a review
Yildiz, K. A., Shin, A. Y., & Kaufman, K. R. (2020) · Journal of NeuroEngineering and Rehabilitation · doi:10.1186/s12984-020-00667-5 · Cited by 113 · see citing works
Optical Stimulation of Neurons
C. Thompson, A., R. Stoddart, P., & Jansen, E. D. (2015) · Current Molecular Imaging · doi:10.2174/2211555203666141117220611 · Cited by 105 · see citing works
“Hirase et al. [6] demonstrated that neurons could be triggered through exposure to pulses of light from a femtosecond laser via a two-photon mechanism.”
BackgroundA shape-memory and spiral light-emitting device for precise multisite stimulation of nerve bundles
Zheng, H., Zhang, Z., Jiang, S., Yan, B., Shi, X., Xie, Y., Huang, X., Yu, Z., Liu, H., Weng, S., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10418-3 · Cited by 58 · see citing works
On the development of optical peripheral nerve interfaces
Anderson, H., & Weir, R. F. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.245461 · Cited by 14 · see citing works
- Authors
- Liske, H., Qian, X., Anikeeva, P., Deisseroth, K., & Delp, S.
- Affiliations
- Stanford University (US)
- Stanford Medicine (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Delp, Scott
- Venue
- Scientific Reports
- Published
- 2013-10-31
- Volume
- 3
- Issue
- 1
- Pages
- 3110-3110
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC3813941
- OpenAlex
- W2148043484
- Cited by
- 42
- References
- 49
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 1 · 2022: 1 · 2020: 7 · 2019: 2 · 2018: 6 · 2017: 4 · 2016: 7 · 2015: 5 · 2014: 5
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- McGill University
- National Institutes of Health
- Stanford Bio-X
- National Institute of General Medical Sciences (T32GM008412)
- National Institute of Neurological Disorders and Stroke (R01NS080954)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- channelrhodopsin-2, optogenetics, neuronal excitation, neuronal inhibition, motor neurons, sciatic nerve, action potential propagation
- MeSH terms
- Channelrhodopsins, Animals, Female, Light, Male, Membrane Potentials, Mice, Transgenic, Neurons, Temperature, Mice
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