High-performance microbial opsins for spatially and temporally precise perturbations of large neuronal networks.

Neuron 2022 Apr 06

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The biophysical properties of existing optogenetic tools constrain the scale, speed, and fidelity of precise optogenetic control. Here, we use structure-guided mutagenesis to engineer opsins that exhibit very high potency while retaining fast kinetics. These new opsins enable large-scale, temporally and spatially precise control of population neural activity. We extensively benchmark these new opsins against existing optogenetic tools and provide a detailed biophysical characterization of a diverse family of opsins under two-photon illumination. This establishes a resource for matching the optimal opsin to the goals and constraints of patterned optogenetics experiments. Finally, by combining these new opsins with optimized procedures for holographic photostimulation, we demonstrate the simultaneous coactivation of several hundred spatially defined neurons with a single hologram and nearly double that number by temporally interleaving holograms at fast rates. These newly engineered opsins substantially extend the capabilities of patterned illumination optogenetic paradigms for addressing neural circuits and behavior. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Savitha Sridharan, Marta A Gajowa, Mora B Ogando, Uday K Jagadisan, Lamiae Abdeladim, Masato Sadahiro, Hayley A Bounds, William D Hendricks, Toby S Turney, Ian Tayler, Karthika Gopakumar, Ian Antón Oldenburg, Stephen G Brohawn, Hillel Adesnik. High-performance microbial opsins for spatially and temporally precise perturbations of large neuronal networks. Neuron. 2022 Apr 06;110(7):1139-1155.e6