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Nat Commun. 2014 Sep 15;5:4894. doi: 10.1038/ncomms5894.

Archaerhodopsin variants with enhanced voltage-sensitive fluorescence in mammalian and Caenorhabditis elegans neurons.

Author information

1
1] Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA [2].
2
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA.
3
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
4
1] Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA [2] Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.

Abstract

Probing the neural circuit dynamics underlying behaviour would benefit greatly from improved genetically encoded voltage indicators. The proton pump Archaerhodopsin-3 (Arch), an optogenetic tool commonly used for neuronal inhibition, has been shown to emit voltage-sensitive fluorescence. Here we report two Arch variants with enhanced radiance (Archers) that in response to 655 nm light have 3-5 times increased fluorescence and 55-99 times reduced photocurrents compared with Arch WT. The most fluorescent variant, Archer1, has 25-40% fluorescence change in response to action potentials while using 9 times lower light intensity compared with other Arch-based voltage sensors. Archer1 is capable of wavelength-specific functionality as a voltage sensor under red light and as an inhibitory actuator under green light. As a proof-of-concept for the application of Arch-based sensors in vivo, we show fluorescence voltage sensing in behaving Caenorhabditis elegans. Archer1's characteristics contribute to the goal of all-optical detection and modulation of activity in neuronal networks in vivo.

PMID:
25222271
PMCID:
PMC4166526
DOI:
10.1038/ncomms5894
[Indexed for MEDLINE]
Free PMC Article

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