Optogenetics
Optogenetics: a decade of illuminating biology
In 2005, a study from the Deisseroth lab published in Nature Neuroscience demonstrated precise and reliable activation of neurons expressing the light-sensitive microbial protein channelrhodopsin-2 in response to pulses of light. This was not the first attempt at controlling neuronal activity with light, but the properties of channelrhodopsin-2 set the stage for its wide adoption. Many neuroscientists have now enthusiastically embraced optogenetics, with long-held views definitively tested and new insights into the brain in both health and disease gained. The optogenetics tool box has rapidly expanded over the past decade, paving the way for experiments that would have once seemed impossible. The reach of optogenetics now extends beyond neuroscience, as the dream of fine-tuned control of cellular activity is not limited to those working on the nervous system.
In this Collection, we present a snapshot of how the field of optogenetics has progressed. While the research and commentaries highlighted in these pages provides only a snippet of this large and robust field, we hope that these articles provide a sense for the technological improvements and biological insights driving the community forward.
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ChR2: Anniversary - The September 2015 issue of Nature Neuroscience celebrates the 10th anniversary of channelrhodopsin-2 in neurons and features articles from the first and senior authors of the original paper along with a Q&A where a number of scientists reflect on the impact of optogenetics.
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News & Comments - Learn about the impact and reach of optogenetics in these news and commentary articles from Nature-branded journals.
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Research - Enjoy an editorially curated selection of articles published in the Nature-branded journals over the past decade, highlighting both tools that were added to the optogenetic toolkit and key biological insights revealed with these approaches.
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Protocols - Browse through an editorially curated selection of experimental protocols related to optogenetics work published in the Nature-branded journals and elsewhere over the past decade.
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Video - Take a guided tour of optogenetics with Nature Video.
Publication timeline for microbial opsins and optogenetics over 45 years. Figure from Deisseroth, K. Optogenetics: 10 years of microbial opsins in neuroscience, September 2015 issue of Nature Neuroscience.
Enjoy an editorially curated selection of articles published in the Nature-branded journals over the past decade, highlighting both tools that were added to the optogenetic toolkit and key biological insights revealed with these approaches.
2005 |
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Technical Report Millisecond-timescale, genetically targeted optical control of neural activity Edward S Boyden, Feng Zhang, Ernst Bamberg, Georg Nagel & Karl Deisseroth Nature Neuroscience, doi:10.1038/nn1525 |
2007 |
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Letter Neural substrates of awakening probed with optogenetic control of hypocretin neurons Antoine R. Adamantidis, Feng Zhang, Alexander M. Aravanis, Karl Deisseroth & Luis de Lecea Nature, doi:10.1038/nature06310 |
Article Multimodal fast optical interrogation of neural circuitry Feng Zhang, Li-Ping Wang, Martin Brauner, Jana F. Liewald, Kenneth Kay, Natalie Watzke, Phillip G. Wood, Ernst Bamberg, Georg Nagel, Alexander Gottschalk & Karl Deisseroth Nature, doi:10.1038/nature05744 |
Technical Report Channelrhodopsin-2–assisted circuit mapping of long-range callosal projections Leopoldo Petreanu, Daniel Huber, Aleksander Sobczyk & Karel Svoboda Nature Neuroscience, doi:10.1038/nn1891 |
2008 |
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Letter Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice Daniel Huber, Leopoldo Petreanu, Nima Ghitani, Sachin Ranade, Tomáš Hromádka, Zach Mainen & Karel Svoboda Nature, doi:10.1038/nature06445 |
Article Optogenetic analysis of synaptic function Jana F Liewald, Martin Brauner, Greg J Stephens, Magali Bouhours, Christian Schultheis, Mei Zhen & Alexander Gottschalk Nature Methods, doi:10.1038/nmeth.1252 |
Article Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration Pamela S Lagali, David Balya, Gautam B Awatramani, Thomas A Münch, Douglas S Kim, Volker Busskamp, Constance L Cepko & Botond Roska Nature Neuroscience, doi:10.1038/nn.2117 |
Technical Report Bi-stable neural state switches André Berndt, Ofer Yizhar, Lisa A Gunaydin, Peter Hegemann & Karl Deisseroth Nature Neuroscience, doi:10.1038/nn.2247 |
2009 |
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Letter Induction of protein-protein interactions in live cells using light Masayuki Yazawa, Amir M Sadaghiani, Brian Hsueh & Ricardo E Dolmetsch Nature Biotechnology, doi:10.1038/nbt.1569 |
Letter Temporally precise in vivo control of intracellular signalling Raag D. Airan, Kimberly R. Thompson, Lief E. Fenno, Hannah Bernstein & Karl Deisseroth Nature, doi:10.1038/nature07926 |
Letter Parvalbumin neurons and gamma rhythms enhance cortical circuit performance Vikaas S. Sohal, Feng Zhang, Ofer Yizhar & Karl Deisseroth Nature, doi:10.1038/nature07991 |
Letter Spatiotemporal control of cell signalling using a light-switchable protein interaction Anselm Levskaya, Orion D. Weiner, Wendell A. Lim & Christopher A. Voigt Nature, doi:10.1038/nature08446 |
Article Driving fast-spiking cells induces gamma rhythm and controls sensory responses Jessica A. Cardin, Marie Carlén, Konstantinos Meletis, Ulf Knoblich, Feng Zhang, Karl Deisseroth, Li-Huei Tsai & Christopher I. Moore Nature, doi:10.1038/nature08002 |
2010 |
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Letter High-performance genetically targetable optical neural silencing by light-driven proton pumps Brian Y. Chow, Xue Han, Allison S. Dobry, Xiaofeng Qian, Amy S. Chuong, Mingjie Li, Michael A. Henninger, Gabriel M. Belfort, Yingxi Lin, Patrick E. Monahan & Edward S. Boyden Nature, doi:10.1038/nature08652 |
Letter Global and local fMRI signals driven by neurons defined optogenetically by type and wiring Jin Hyung Lee, Remy Durand, Viviana Gradinaru, Feng Zhang, Inbal Goshen, Dae-Shik Kim, Lief E. Fenno, Charu Ramakrishnan & Karl Deisseroth Nature, doi:10.1038/nature09108 |
Letter Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry Alexxai V. Kravitz, Benjamin S. Freeze, Philip R. L. Parker, Kenneth Kay, Myo T. Thwin, Karl Deisseroth & Anatol C. Kreitzer Nature, doi:10.1038/nature09159 |
Brief Communication Optogenetic control of heart muscle in vitro and in vivo Tobias Bruegmann, Daniela Malan, Michael Hesse, Thomas Beiert, Christopher J Fuegemann, Bernd K Fleischmann & Philipp Sasse Nature Methods, doi:10.1038/nmeth.1512 |
Technical Report Orderly recruitment of motor units under optical control in vivo Michael E Llewellyn, Kimberly R Thompson, Karl Deisseroth & Scott L Delp Nature Medicine, doi:10.1038/nm.2228 |
Technical Report Ultrafast optogenetic control Lisa A Gunaydin, Ofer Yizhar, André Berndt, Vikaas S Sohal, Karl Deisseroth & Peter Hegemann Nature Neuroscience, doi:10.1038/nn.2495 |
2011 |
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Letter Amygdala circuitry mediating reversible and bidirectional control of anxiety Kay M. Tye, Rohit Prakash, Sung-Yon Kim, Lief E. Fenno, Logan Grosenick, Hosniya Zarabi, Kimberly R. Thompson, Viviana Gradinaru, Charu Ramakrishnan & Karl Deisseroth Nature, doi:10.1038/nature09820 |
Brief Communication Selective optical drive of thalamic reticular nucleus generates thalamic bursts and cortical spindles Michael M Halassa, Joshua H Siegle, Jason T Ritt, Jonathan T Ting, Guoping Feng & Christopher I Moore Nature Neuroscience, doi:10.1038/nn.2880 |
Article AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training Yexica Aponte, Deniz Atasoy & Scott M Sternson Nature Neuroscience, doi:10.1038/nn.2739 |
Article Functional identification of an aggression locus in the mouse hypothalamus Dayu Lin, Maureen P. Boyle, Piotr Dollar, Hyosang Lee, E. S. Lein, Pietro Perona & David J. Anderson Nature, doi:10.1038/nature09736 |
Article Neocortical excitation/inhibition balance in information processing and social dysfunction Ofer Yizhar, Lief E. Fenno, Matthias Prigge, Franziska Schneider, Thomas J. Davidson, Daniel J. O’Shea, Vikaas S. Sohal, Inbal Goshen, Joel Finkelstein, Jeanne T. Paz, Katja Stehfest, Roman Fudim, Charu Ramakrishnan, John R. Huguenard, Peter Hegemann & Karl Deisseroth Nature, doi:10.1038/nature10360 |
Technical Report Ultra light-sensitive and fast neuronal activation with the Ca2+-permeable channelrhodopsin CatCh Sonja Kleinlogel, Katrin Feldbauer, Robert E Dempski, Heike Fotis, Phillip G Wood, Christian Bamann & Ernst Bamberg Nature Neuroscience, doi:10.1038/nn.2776 |
Technical Report An optogenetic toolbox designed for primates Ilka Diester, Matthew T Kaufman, Murtaza Mogri, Ramin Pashaie, Werapong Goo, Ofer Yizhar, Charu Ramakrishnan, Karl Deisseroth & Krishna V Shenoy Nature Neuroscience, doi:10.1038/nn.2749 |
2012 |
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Letter Optogenetic stimulation of a hippocampal engram activates fear memory recall Xu Liu, Steve Ramirez, Petti T. Pang, Corey B. Puryear, Arvind Govindarajan, Karl Deisseroth & Susumu Tonegawa Nature, doi:10.1038/nature11028 |
Brief Communication Distinct roles for direct and indirect pathway striatal neurons in reinforcement Alexxai V Kravitz, Lynne D Tye & Anatol C Kreitzer Nature Neuroscience, doi:10.1038/nn.3100 |
Brief Communication Saccadic eye movements evoked by optogenetic activation of primate V1 Mehrdad Jazayeri, Zachary Lindbloom-Brown & Gregory D Horwitz Nature Neuroscience, doi:10.1038/nn.3210 |
Article Control of timing, rate and bursts of hippocampal place cells by dendritic and somatic inhibition Sébastien Royer, Boris V Zemelman, Attila Losonczy, Jinhyun Kim, Frances Chance, Jeffrey C Magee & György Buzsáki Nature Neuroscience, doi:10.1038/nn.3077 |
Article Crystal structure of the channelrhodopsin light-gated cation channel Hideaki E. Kato, Feng Zhang, Ofer Yizhar, Charu Ramakrishnan, Tomohiro Nishizawa, Kunio Hirata, Jumpei Ito, Yusuke Aita, Tomoya Tsukazaki, Shigehiko Hayashi, Peter Hegemann, Andrés D. Maturana, Ryuichiro Ishitani, Karl Deisseroth & Osamu Nureki Nature, doi:10.1038/nature10870 |
Article Input-specific control of reward and aversion in the ventral tegmental area Stephan Lammel, Byung Kook Lim, Chen Ran, Kee Wui Huang, Michael J. Betley, Kay M. Tye, Karl Deisseroth & Robert C. Malenka Nature, doi:10.1038/nature11527 |
Resource A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing Linda Madisen, Tianyi Mao, Henner Koch, Jia-min Zhuo, Antal Berenyi, Shigeyoshi Fujisawa, Yun-Wei A Hsu, Alfredo J Garcia III, Xuan Gu, Sebastien Zanella, Jolene Kidney, Hong Gu, Yimei Mao, Bryan M Hooks, Edward S Boyden, György Buzsáki, Jan Marino Ramirez, Allan R Jones, Karel Svoboda, Xue Han, Eric E Turner & Hongkui Zeng Nature Neuroscience, doi:10.1038/nn.3078 |
2013 |
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Letter Optical control of mammalian endogenous transcription and epigenetic states Silvana Konermann, Mark D. Brigham, Alexandro Trevino, Patrick D. Hsu, Matthias Heidenreich, Le Cong, Randall J. Platt, David A. Scott, George M. Church & Feng Zhang Nature, doi:10.1038/nature12466 |
Article On-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy Esther Krook-Magnuson, Caren Armstrong, Mikko Oijala & Ivan Soltesz Nature Communications, doi:10.1038/ncomms2376 |
Article Holographic optogenetic stimulation of patterned neuronal activity for vision restoration Inna Reutsky-Gefen, Lior Golan, Nairouz Farah, Adi Schejter, Limor Tsur, Inbar Brosh & Shy Shoham Nature Communications, doi:10.1038/ncomms2500 |
Article Closed-loop optogenetic control of thalamus as a tool for interrupting seizures after cortical injury Jeanne T Paz, Thomas J Davidson, Eric S Frechette, Bruno Delord, Isabel Parada, Kathy Peng, Karl Deisseroth & John R Huguenard Nature Neuroscience, doi:10.1038/nn.3269 |
Article Neural coding during active somatosensation revealed using illusory touch Daniel H O'Connor, S Andrew Hires, Zengcai V Guo, Nuo Li, Jianing Yu, Qian-Quan Sun, Daniel Huber & Karel Svoboda Nature Neuroscience, doi:10.1038/nn.3419 |
Article A causal link between prediction errors, dopamine neurons and learning Elizabeth E Steinberg, Ronald Keiflin, Josiah R Boivin, Ilana B Witten, Karl Deisseroth & Patricia H Janak Nature Neuroscience, doi:10.1038/nn.3413 |
Article Inhibition of inhibition in visual cortex: the logic of connections between molecularly distinct interneurons Carsten K Pfeffer, Mingshan Xue, Miao He, Z Josh Huang & Massimo Scanziani Nature Neuroscience, doi:10.1038/nn.3446 |
Technical Report ReaChR: a red-shifted variant of channelrhodopsin enables deep transcranial optogenetic excitation John Y Lin, Per Magne Knutsen, Arnaud Muller, David Kleinfeld & Roger Y Tsien Nature Neuroscience, doi:10.1038/nn.3502 |
2014 |
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Letter Virally mediated optogenetic excitation and inhibition of pain in freely moving nontransgenic mice Shrivats Mohan Iyer, Kate L Montgomery, Chris Towne, Soo Yeun Lee, Charu Ramakrishnan, Karl Deisseroth & Scott L Delp Nature Biotechnology, doi:10.1038/nbt.2834 |
Article Independent optical excitation of distinct neural populations Nathan C Klapoetke, Yasunobu Murata, Sung Soo Kim, Stefan R Pulver, Amanda Birdsey-Benson, Yong Ku Cho, Tania K Morimoto, Amy S Chuong, Eric J Carpenter, Zhijian Tian, Jun Wang, Yinlong Xie, Zhixiang Yan, Yong Zhang, Brian Y Chow, Barbara Surek, Michael Melkonian, Vivek Jayaraman, Martha Constantine-Paton, Gane Ka-Shu Wong & Edward S Boyden Nature Methods, doi:10.1038/nmeth.2836 |
Article All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins Daniel R Hochbaum, Yongxin Zhao, Samouil L Farhi, Nathan Klapoetke, Christopher A Werley, Vikrant Kapoor, Peng Zou, Joel M Kralj, Dougal Maclaurin, Niklas Smedemark-Margulies, Jessica L Saulnier, Gabriella L Boulting, Christoph Straub, Yong Ku Cho, Michael Melkonian, Gane Ka-Shu Wong, D Jed Harrison, Venkatesh N Murthy, Bernardo L Sabatini, Edward S Boyden, Robert E Campbell & Adam E Cohen Nature Methods, doi:10.1038/nmeth.3000 |
Technical Report Noninvasive optical inhibition with a red-shifted microbial rhodopsin Amy S Chuong, Mitra L Miri, Volker Busskamp, Gillian A C Matthews, Leah C Acker, Andreas T Sørensen, Andrew Young, Nathan C Klapoetke, Mike A Henninger, Suhasa B Kodandaramaiah, Masaaki Ogawa, Shreshtha B Ramanlal, Rachel C Bandler, Brian D Allen, Craig R Forest, Brian Y Chow, Xue Han, Yingxi Lin, Kay M Tye, Botond Roska, Jessica A Cardin & Edward S Boyden Nature Neuroscience, doi:10.1038/nn.3752 |
Technical Report Simultaneous cellular-resolution optical perturbation and imaging of place cell firing fields John Peter Rickgauer, Karl Deisseroth & David W Tank Nature Neuroscience, doi:10.1038/nn.3866 |
2015 |
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Letter Optogenetics enables functional analysis of human embryonic stem cell–derived grafts in a Parkinson's disease model Julius A Steinbeck, Se Joon Choi, Ana Mrejeru, Yosif Ganat, Karl Deisseroth, David Sulzer, Eugene V Mosharov & Lorenz Studer Nature Biotechnology, doi:10.1038/nbt.3124 |
