Optogenetics: molecules enabling neural control by light
We have pioneered the development of fully genetically encoded reagents that, when targeted to specific cells, enable their physiology to be controlled via light. These reagents, known as optogenetic tools, enable temporally precise control of neural electrical activity, cellular signaling, and other high-speed physiological processes using light. Such tools are in widespread use in neuroscience and bioengineering, for the study of how specific neurons contribute to cognition, emotion, and movement, and to brain disorder states, or to the remedy thereof. These tools are also being evaluated as components of prototype optical neural control prosthetics for ultraprecise treatment of intractable brain disorders. Derived from the natural world, these tools highlight the power of ecological diversity, in yielding technologies for analyzing biological complexity and addressing human health. We distribute these tools as freely as possible to the scientific community.
Resources
Accessory plasmids for optogenetics
Arch: archaerhodopsin (light-driven proton pump)
ArchT: light-sensitive archaerhodopsin
ChR2-2A-Halo: channelrhodopsin-halorhodopsin gene fusions
ChR2: channelrhodopsin-2 (light-driven cation channel)
Chrimson: red light-drivable channelrhodopsin
ChromeQ: optogenetic activation with reduced proton and calcium currents
Chronos: high-speed, light-sensitive, channelrhodopsin
CoChR: large-current channelrhodopsin
Glial optogenetic tools
Halo/NpHR: halorhodopsin (light-driven chloride pump)
Jaws: red light-drivable halorhodopsin
Lentivirus production for high-titer, cell-specific, in vivo neural labeling
Lumitoxins: light-actuated tethered toxin architecture
Mac: light-driven proton pump of L. maculans
soCoChR: soma-targeted, high-amplitude channelrhodopsin
Publications
Optogenetic Control of Neural Activity: the Biophysics of Microbial Rhodopsins in Neuroscience
Quarterly Reviews of Biophysics | 2023Piatkevich KD, Boyden ES (2023) Optogenetic Control of Neural Activity: the Biophysics of Microbial Rhodopsins in Neuroscience, Quarterly Review of Biophysics 13:1-81.
An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques
Neuron | 2020Gong X, Mendoza-Halliday D, Ting JT, Kaiser T, Sun X, Bastos AM, Wimmer RD, Guo B, Chen Q, Zhou Y, Pruner M, Wu CW, Park D, Deisseroth K, Barak B, Boyden ES, Miller EK, Halassa MM, Fu Z, Bi G, Desimone R, Feng G (2020) An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques, Neuron 107(1):38-51.
Optogenetics: Tools for Controlling Brain Cells with Light
Molecular Frontiers Journal | 2019Edward S. Boyden (2019) Optogenetics: Tools for Controlling Brain Cells with Light, Molecular Frontiers Journal, 3(2)129-137.
Investigating the feasibility of channelrhodopsin variants for nanoscale optogenetics
Neurophotonics | 2019Markus A. Stahlberg, Charu Ramakrishnan, Katrin I. Willig, Edward S. Boyden, Karl Deisseroth, Camin Dean (2019) Investigating the feasibility of channelrhodopsin variants for nanoscale optogenetics, Neurophotonics 6(1):015007.
Melanopsin for precise optogenetic activation of astrocyte-neuron networks
Glia | 2019Sara Mederos, Alicia Hernández‐Vivanco, Jorge Ramírez‐Franco, Mario Martín‐Fernández, Marta Navarrete, Aimei Yang, Edward S. Boyden, Gertrudis Perea (2019) Melanopsin for precise optogenetic activation of astrocyte‐neuron networks, Glia 67(5):915-934.
Multidimensional screening yields channelrhodopsin variants having improved photocurrent and order-of-magnitude reductions in calcium and proton currents
Journal of Biological Chemistry | 2019Cho YK, Park D*, Yang A*, Chen F, Chuong AS, Klapoetke NC, Boyden ES (2019) Multidimensional screening yields channelrhodopsin variants having improved photocurrent and order-of-magnitude reductions in calcium and proton currents, Journal of Biological Chemistry 294(11):3806-3821. (*, equal contribution)
A Suite of Transgenic Driver and Reporter Mouse Lines with Enhanced Brain-Cell-Type Targeting and Functionality
Cell | 2018Daigle TL, Madisen L, Hage TA, Valley MT, Knoblich U, Larsen RS, Takeno MM, Huang L, Gu H, Larsen R, Mills M, Bosma-Moody A, Siverts LA, Walker M, Graybuck LT, Yao Z, Fong O, Nguyen TN, Garren E, Lenz GH, Chavarha M, Pendergraft J, Harrington J, Hirokawa KE, Harris JA, Nicovich PR, McGraw MJ, Ollerenshaw DR, Smith KA, Baker CA, Ting JT, Sunkin SM, Lecoq J, Lin MZ, Boyden ES, Murphy GJ, da Costa NM, Waters J, Li L, Tasic B, Zeng H (2018) A Suite of Transgenic Driver and Reporter Mouse Lines with Enhanced Brain-Cell-Type Targeting and Functionality, Cell 174(2):465-480.
Temporally precise single-cell resolution optogenetics
Nature Neuroscience | 2017Or A. Shemesh*, Dimitrii Tanese*, Valeria Zampini*, Changyang Linghu, Kiryl Piatkevich, Emiliano Ronzitti, Eirini Papagiakoumou, Edward S. Boyden+ and Valentina Emiliani+ (2017) Temporally precise single-cell resolution optogenetics, Nature Neuroscience 20:1796–1806. (*, co-first authors; +, co-corresponding authors)
Functional and topological diversity of LOV domain photoreceptors
Proceedings of the National Academy of Sciences | 2016Glantz, S.T., Carpenter, E.J., Melkonian, M., Gardner, K.H., Boyden, E.S., Wong, G. K.-S., Chow, B.Y. (2016) Functional and topological diversity of LOV domain photoreceptors, Proceedings of the National Academy of Sciences, 113(11):E1442–E1451.
Optogenetics and the future of neuroscience
Nature Neuroscience | 2015Boyden, E. S. (2015) Optogenetics and the future of neuroscience (Overview, Optogenetics 10th Anniversary Issue), Nature Neuroscience 18:1200–1201.
Transgenic Mice for Intersectional Targeting of Neural Sensors and Effectors with High Specificity and Performance
Neuron | 2015Madisen, L., Garner, A.R., Shimaoka, D., Chuong, A.S., Klapoetke, N.C., Li, L., van der Bourg, A., Niino, Y., Egolf, L., Monetti, C., Gu, H., Mills, M., Cheng, A., Tasic, B., Nguyen, T.N., Sunkin, S.M., Benucci, A., Nagy, A., Miyawaki, A., Helmchen, F., Empson, R.M., Knöpfel, T., Boyden, E.S., Reid, R.C., Carandini, M., Zeng, H. (2015) Transgenic Mice for Intersectional Targeting of Neural Sensors and Effectors with High Specificity and Performance, Neuron 85(5):889-892.
Let there be light
cientific American Mind | 2014Boyden, E. S. (2014) Let there be light, Scientific American Mind, November/December 2014.
Noninvasive optical inhibition with a red-shifted microbial rhodopsin
Nature Neuroscience | 2014Chuong, A. S., Miri, M. L.*, Busskamp, V.*, Matthews, G.A.C.*, Acker, L.C.*, Soresnsen, A.T., Young, A., Klapoetke, N. C., Henninger, M.A., Kodandaramaiah, S.B., Ogawa, M., Ramanlal, S. B., Bandler, R. C., Allen, B. D., Forest, C.R., Chow, B.Y., Han, X., Lin, Y., Tye, K.M., Roska, B., Cardin, J.A., Boyden, E. S. (2014) Noninvasive optical inhibition with a red-shifted microbial rhodopsin, Nature Neuroscience 17:1123-1129. (*, equal contribution)
Independent Optical Excitation of Distinct Neural Populations
Nature Methods | 2014Klapoetke, 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., Wang, J., Xie, Y., Yan, Z., Zhang, Y., Chow, B.Y., Surek, B., Melkonian, M., Jayaraman, V., Constantine-Paton, M., Wong, G. K.*, Boyden, E. S.* (2014) Independent Optical Excitation of Distinct Neural Populations, Nature Methods 11:338–346. (* co-corresponding authors)
A fully genetically-encoded protein architecture for optical control of peptide ligand concentration
Nature Communications | 2014Schmidt, D., Tillberg, P. W.*, Chen, F.*, Boyden, E. S. (2014) A fully genetically-encoded protein architecture for optical control of peptide ligand concentration, Nature Communications, 5:3019. (* equal contribution)
A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing
Nature Neuroscience | 2012Madisen, L., Mao, T., Koch, H., Zhuo, J.-m., Berenyi, A., Fujisawa, S., Hsu, Y.-W., Garcia, A. J., Gu, X., Zanella, S., Kidney, J., Gu, H., Mao, Y., Hooks, B. M., Boyden, E. S., Buzsáki, G., Ramirez, J. M., Jones, A. R., Svoboda, K., Han, X., Turner, E. E., Zeng, H. (2012) A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing, Nature Neuroscience 15(5):793-802.
Genetically encoded molecular tools for light-driven silencing of targeted neurons
Progress in Brain Research | 2012Chow B.Y., Han, X., Boyden, E. S. (2012) Genetically encoded molecular tools for light-driven silencing of targeted neurons, Progress in Brain Research 196:49-61.
Tools for observing and controlling specific molecular or physiological pathways in intact cells and tissues. Preface
Progress in Brain Research | 2012Knopfel, T., Boyden, E. S. (2012) Tools for observing and controlling specific molecular or physiological pathways in intact cells and tissues. Preface, Progress in Brain Research 196:vii–viii.
Optogenetics: Tools for Controlling and Monitoring Neuronal Activity
Progress in Brain Research | 2012T. Knopfel and E. Boyden, eds. (2012) Optogenetics: Tools for Controlling and Monitoring Neuronal Activity, Progress in Brain Research, vol. 196, Elsevier.
Light-Activated Ion Pumps and Channels for Temporally Precise Optical Control of Activity in Genetically Targeted Neurons
Neuromethods Series | 2012Chow, B. Y., Han, X., Bernstein, J. G., Monahan, P. E., Boyden, E. S. (2012) Light-Activated Ion Pumps and Channels for Temporally Precise Optical Control of Activity in Genetically Targeted Neurons, p. 305-338, Neuronal Network Analysis: Concepts and Experimental Approaches, edited by Tommaso Fellin and Michael Halassa,Neuromethods Series Volume 67, Humana Press.
Optogenetic tools for analyzing the neural circuits of behavior
Trends in Cognitive Sciences | 2011Bernstein, J. G., Boyden, E. S. (2011) Optogenetic tools for analyzing the neural circuits of behavior, Trends in Cognitive Sciences 15(12):592-600.
A gene-fusion strategy for stoichiometric and co-localized expression of light-gated membrane proteins
Nature Methods | 2011Kleinlogel, S., Terpitz, U., Legrum, B., Gokbuget, D., Boyden, E. S., Bamann, C., Wood, P. G., Bamberg, E. (2011) A gene-fusion strategy for stoichiometric and co-localized expression of light-gated membrane proteins, Nature Methods 8(12):1083-1088.
Optogenetics and thermogenetics: technologies for controlling the activity of targeted cells within intact neural circuits
Current Opinion in Neurobiology | 2011Bernstein, J. G., Garrity, P. A.*, Boyden, E. S.* (2012) Optogenetics and thermogenetics: technologies for controlling the activity of targeted cells within intact neural circuits, Current Opinion in Neurobiology 22(1):61-71. (* co-corresponding authors)
Optogenetics: Using Light to Control the Brain
Cerebrum | 2011Boyden ES. (2011) Optogenetics: using light to control the brain, Cerebrum 2011:16.
Towards Optogenetic Sensory Replacement
Conference Proceedings of the IEEE Engineering in Medicine and Biology Society | 2011Doroudchi, M. M., Greenberg, K. P., Zorzos, A. N., Hauswirth, W. W., Fonstad, C. G., Horsager, A., Boyden, E. S. (2011) Towards Optogenetic Sensory Replacement, Conference Proceedings of the IEEE Engineering in Medicine and Biology Society 2011:3139-41.
Optogenetics
33rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society | 2011Boyden, E. S. (2011) Optogenetics. 33rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC ’11).
The Birth of Optogenetics
The Scientist | 2011Boyden, E. S. (2011) The Birth of Optogenetics, The Scientist, July 2011 Issue. (Cover Story.)
Synthetic Physiology
Science | 2011Chow, B. Y. and Boyden, E. S. (2011) Synthetic Physiology, Science 332(6037):1508-1509.
Synthetic Physiology: Strategies for Adapting Tools from Nature for Genetically-Targeted Control of Fast Biological Processes
Methods in Enzymology | 2011Chow, B. Y.*, Chuong, A. S. *, Klapoetke, N. C. *, Boyden, E. S. (2011) Synthetic Physiology: Strategies for Adapting Tools from Nature for Genetically-Targeted Control of Fast Biological Processes, Methods in Enzymology 497:425-43. (* co-first authors)
A history of optogenetics: the development of tools for controlling brain circuits with light
F1000 Biology Reports | 2011Boyden, E.S. (2011) A history of optogenetics: the development of tools for controlling brain circuits with light, F1000 Biology Reports 3:11.
A high-light sensitivity optical neural silencer: development, and application to optogenetic control of nonhuman primate cortex
Frontiers in Systems Neuroscience | 2011Han, X.*, Chow, B. Y.*, Zhou, H., Klapoetke, N. C., Chuong, A., Rajimehr, R., Yang, A., Baratta, M. V., Winkle, J., Desimone, R., Boyden, E. S. (2011) A high-light sensitivity optical neural silencer: development and application to optogenetic control of non-human primate cortex, Frontiers in Systems Neuroscience 5:18. (* co-first authors)
Light-Activated Ion Pumps and Channels for Temporally Precise Optical Control of Activity in Genetically Targeted Neurons
Neuromethods | 2011Chow, B. Y., Han, X., Bernstein, J. G., Monahan, P. E., Boyden, E. S. (2011) Light-Activated Ion Pumps and Channels for Temporally Precise Optical Control of Activity in Genetically Targeted Neurons, Chapter 6, Photosensitive Molecules for Controlling Biological Function, edited by James J. Chambers and Richard H. Kramer, Neuromethods Series Volume 55, Humana Press.
Toward the Second Generation of Optogenetic Tools
Journal of Neuroscience | 2010Knopfel, T., Lin, M. Z., Levskaya, A., Tian, L., Lin, J. Y., Boyden, E. S. (2010) Toward the Second Generation of Optogenetic Tools, Journal of Neuroscience 30(45):14998-15004.
Molecular Tools for Controlling Brain Circuits with Light
Science Magazine | 2010Boyden, E. S. (2010) "Molecular Tools for Controlling Brain Circuits with Light," Eppendorf and Science Prize for Neurobiology Competition Essay, Science Magazine.
Controlling the brain with light
SPIE Newsroom | 2010Boyden, E. S. (2010) Controlling the Brain with Light. SPIE Newsroom. 6/10/2010.
Defining An Algorithm For Inventing From Nature
Technology Review | 2010Boyden, E. S. and Chow, B. Y. (2010) "Defining An Algorithm For Inventing From Nature." Column, Technology Review. 1/19/2010.
High-performance genetically targetable optical neural silencing by light-driven proton pumps
Nature | 2010Chow, B. Y.*, Han, X.*, Dobry, A. S., Qian, X., Chuong, A. S., Li, M., Henninger, M. A., Belfort, G. M., Lin, Y., Monahan, P. E., Boyden, E. S. (2010) High-performance genetically targetable optical neural silencing by light- driven proton pumps, Nature 463:98-102. (* co-first authors)
Informational Lesions: Optical Perturbation of Spike Timing and Neural Synchrony Via Microbial Opsin Gene Fusions
Frontiers in Molecular Neuroscience | 2009Han X., Qian X., Stern P., Chuong A. and Boyden E.S. (2009) Informational Lesions: Optical Perturbation of Spike Timing and Neural Synchrony Via Microbial Opsin Gene Fusions, Frontiers in Molecular Neuroscience 2:12.
Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution
PLoS ONE | 2007Han, X. and Boyden, E. S. (2007) Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution, PLoS ONE 2(3): p. e299.
Channelrhodopsin-2 and optical control of excitable cells
Nature Methods | 2006Zhang, F., Wang, L.-P., Boyden, E. S., Deisseroth, K. (2006) Optical control of excitable cells and Channelrhodopsin-2, Nature Methods 3(10):785-92.
Millisecond-timescale, genetically-targeted optical control of neural activity
Nature Neuroscience | 2005Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G., Deisseroth, K. (2005) Millisecond-timescale, genetically-targeted optical control of neural activity, Nature Neuroscience 8(9):1263-1268.