WAChRs are excitatory opsins sensitive to indoor lighting

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Abstract Hundreds of novel opsins have been characterized since the advent of optogenetics, but low experimental throughput has limited the scale of opsin engineering campaigns. We modified an automated patch-clamp system with a multispectral light source and a custom light path to enable high-throughput electrophysiological measurements of opsin functional properties. Using this approach, we screened over 1,750 opsins from a range of families. We discovered that the F240A mutation of the light-gated potassium channel WiChR abolished potassium selectivity, turning it into a sensitive excitatory channel that we dubbed “WAChR”. We systematically mutated WAChR and identified variants that expand the frontier of speed-sensitivity tradeoffs. Multiple WAChR variants produced large inward currents in response to indoor ambient office light, and responded to irradiances as low as 15 nW/mm 2 , something that we did not observe with other ultra-sensitive opsins. In vivo recording from the mouse cortex confirmed that WAChRs exhibit enhanced sensitivity in neurons. These ambient-light sensitive channels should be broadly useful for neuroscience research and vision restoration therapies.

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