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Bi-stable neural state switches

Nature Neuroscience volume 12, pages 229–234 (2009)Cite this article

Abstract

Here we describe bi-stable channelrhodopsins that convert a brief pulse of light into a stable step in membrane potential. These molecularly engineered probes nevertheless retain millisecond-scale temporal precision. Photocurrents can be precisely initiated and terminated with different colors of light, but operate at vastly longer time scales than conventional channelrhodopsins as a result of modification at the C128 position that extends the lifetime of the open state. Because of their enhanced kinetic stability, these step-function tools are also effectively responsive to light at orders of magnitude lower intensity than wild-type channelrhodopsins. These molecules therefore offer important new capabilities for a broad range of in vivo applications.

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Figure 1: Step-function optogenetics: C128 mutations.
Figure 2: Precise step termination with red-shifted light.
Figure 3: SFO genes in neurons.
Figure 4: Bi-stable switching behavior in neurons.

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Acknowledgements

A.B. is supported by a Leibniz Graduate School fellowship, O.Y. by an European Molecular Biology Organization long-term postdoctoral fellowship and L.A.G. by a Stanford Bio-X Graduate Fellowship. P.H. is supported by the Deutsche Forschungsgemeinschaft (SFB498 and CoE: Unifying concepts in Catalysis). K.D. is supported by the California Institute of Regenerative Medicine, the McKnight and Wallace H. Coulter Foundations, the National Science Foundation, the US National Institute of Mental Health, the US National Institute on Drug Abuse, the US National Institutes of Health Pioneer Award, and the Kinetics and Keck Foundations.

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Author notes

  1. André Berndt, Ofer Yizhar and Lisa A Gunaydin: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Biology, Experimental Biophysics, Humboldt-University, Invalidenstraße 42, Berlin, D-10115, Germany

    André Berndt & Peter Hegemann

  2. Department of Bioengineering, Behavioral Sciences, W083 Clark Center,

    Ofer Yizhar, Lisa A Gunaydin & Karl Deisseroth

  3. 318 Campus Drive West, Stanford University, Stanford, 94305, California, USA

    Ofer Yizhar, Lisa A Gunaydin & Karl Deisseroth

  4. Neuroscience Program, Behavioral Sciences, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, 94305, California, USA

    Lisa A Gunaydin

  5. Department of Psychiatry and Behavioral Sciences, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, 94305, California, USA

    Karl Deisseroth

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Berndt, A., Yizhar, O., Gunaydin, L. et al. Bi-stable neural state switches. Nat Neurosci 12, 229–234 (2009). https://doi.org/10.1038/nn.2247

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