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  • Historical Commentary
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Optogenetics: 10 years of microbial opsins in neuroscience

Nature Neuroscience volume 18, pages 1213–1225 (2015)Cite this article

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Abstract

Over the past 10 years, the development and convergence of microbial opsin engineering, modular genetic methods for cell-type targeting and optical strategies for guiding light through tissue have enabled versatile optical control of defined cells in living systems, defining modern optogenetics. Despite widespread recognition of the importance of spatiotemporally precise causal control over cellular signaling, for nearly the first half (2005–2009) of this 10-year period, as optogenetics was being created, there were difficulties in implementation, few publications and limited biological findings. In contrast, the ensuing years have witnessed a substantial acceleration in the application domain, with the publication of thousands of discoveries and insights into the function of nervous systems and beyond. This Historical Commentary reflects on the scientific landscape of this decade-long transition.

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Figure 1: The biochemical foundations of the study of microbial light-activated proteins.
Figure 2: Putting the pieces together.
Figure 3: Progress in genetically guided intervention for optogenetics.
Figure 4: Progress in activity-guided intervention for optogenetics.
Figure 5: Progress in spatially guided intervention for optogenetics: beyond cell subpopulation or projection targeting.
Figure 6: Variations on the theme.
Figure 7: Publication timeline for microbial opsins and optogenetics over 45 years.

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Acknowledgements

I am deeply grateful to all of our collaborators and lab members from the first 5 years of optogenetics development (for more on these scientists, see http://www.scientificamerican.com/article/optogenetics-controlling/) to the present (http://web.stanford.edu/group/dlab/group_members.html), and to the funders who supported the lab from the earliest time, corresponding to Figure 2a (http://optogenetics.org/funding/), to the present. From those early years there were wonderful collaborations with P. Hegemann and L. de Lecea, and I am notably grateful to G. Nagel for promptly sending the initial channelrhodopsin clone in response to my e-mail request. I am also grateful for discussions, experiments and analysis with all of the students and postdoctoral fellows, including, for ref. 2, E. Boyden and F. Zhang; for Figure 1, F. Zhang, A. Berndt, V. Gradinaru, S.Y. Lee, C. Ramakrishnan and L. Stryer; and for Figure 2b–e, F. Zhang as well as A. Adamantidis, A. Aravanis, E. Boyden, L. Grosenick, S.Y. Lee and L. Wang. Tools and reagents developed are freely available (http://www.optogenetics.org/, http://addgene.org/).

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Authors and Affiliations

  1. Karl Deisseroth is in the Departments of Bioengineering and of Psychiatry and Behavioral Sciences and the Howard Hughes Medical Institute, Stanford University, Stanford, California, USA.,

    Karl Deisseroth

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Supplementary Video 1

Optogenetic mouse behavioral modulation. Initial optogenetic behavioral control in mammals with the fiber-optic neural interface. Stimulation of the right anterior motor cortex in a Thy1::ChR2-EYFP transgenic mouse35,36 with 20-Hz blue light flashes elicits contralateral circling. Mouse line generated with support of the US National Institute of Mental Health (principal investigators G. Feng, G. Augustine and K. Deisseroth). Recorded 14 July 2007 by F. Zhang, Deisseroth laboratory, Stanford University. (MOV 2431 kb)

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Deisseroth, K. Optogenetics: 10 years of microbial opsins in neuroscience. Nat Neurosci 18, 1213–1225 (2015). https://doi.org/10.1038/nn.4091

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