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Dual-color optical activation and suppression of neurons with high temporal precision

Noëmie Mermet-Joret, Andrea Moreno, Agnieszka Zbela, Bárður Eyjólfsson Ellendersen, Nathalie Krauth, Anne von Philipsborn, Joaquin Piriz, John Y. Lin, View ORCID ProfileSadegh Nabavi
doi: https://doi.org/10.1101/2021.05.05.442824
Noëmie Mermet-Joret
1DANDRITE, The Danish Research Institute of Translational Neuroscience, Aarhus University, Denmark
2Department of Molecular Biology and Genetics, Aarhus University, Denmark
3Center for Proteins in Memory - PROMEMO, Danish National Research Foundation
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Andrea Moreno
1DANDRITE, The Danish Research Institute of Translational Neuroscience, Aarhus University, Denmark
2Department of Molecular Biology and Genetics, Aarhus University, Denmark
3Center for Proteins in Memory - PROMEMO, Danish National Research Foundation
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Agnieszka Zbela
4Tasmanian School of Medicine, College of Health and Medicine, University of Tasmania, Tasmania, TAS 7000, Australia
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Bárður Eyjólfsson Ellendersen
1DANDRITE, The Danish Research Institute of Translational Neuroscience, Aarhus University, Denmark
2Department of Molecular Biology and Genetics, Aarhus University, Denmark
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Nathalie Krauth
1DANDRITE, The Danish Research Institute of Translational Neuroscience, Aarhus University, Denmark
2Department of Molecular Biology and Genetics, Aarhus University, Denmark
3Center for Proteins in Memory - PROMEMO, Danish National Research Foundation
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Anne von Philipsborn
1DANDRITE, The Danish Research Institute of Translational Neuroscience, Aarhus University, Denmark
2Department of Molecular Biology and Genetics, Aarhus University, Denmark
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Joaquin Piriz
5Instituto de Fisiología Biología Molecular y Neurociencias (IFIBYNE), Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina
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John Y. Lin
4Tasmanian School of Medicine, College of Health and Medicine, University of Tasmania, Tasmania, TAS 7000, Australia
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  • For correspondence: john.lin@utas.edu.au snabavi@dandrite.au.dk
Sadegh Nabavi
1DANDRITE, The Danish Research Institute of Translational Neuroscience, Aarhus University, Denmark
2Department of Molecular Biology and Genetics, Aarhus University, Denmark
3Center for Proteins in Memory - PROMEMO, Danish National Research Foundation
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  • ORCID record for Sadegh Nabavi
  • For correspondence: john.lin@utas.edu.au snabavi@dandrite.au.dk
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Abstract

A fundamental challenge in the optogenetic toolbox is that all opsins, regardless of their excitation spectra, are activated by blue light. We hypothesized that pairing a red-shifted channelrhodopsin with a blue light-sensitive anion channel of appropriately matching kinetics shall render neurons responsive to a red but not blue light. To achieve this, we used a semi-rational mutagenesis strategy to optimize the kinetics and light spectrum of a chloride channelrhodopsin. By pairing optimized variants of blue light-sensitive anion channel ZipACR with vfChrimson, a fast red-shifted channelrhodopsin, we created a system in which red light derives precise and faithful action potentials of high frequencies, while blue light, through shunting inhibition, nullifies the effect of the red-shifted ChR2. Additionally, by a simple switch between red and blue lights, one can effectively excite or inhibit the activity of the same neurons.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 06, 2021.
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Dual-color optical activation and suppression of neurons with high temporal precision
Noëmie Mermet-Joret, Andrea Moreno, Agnieszka Zbela, Bárður Eyjólfsson Ellendersen, Nathalie Krauth, Anne von Philipsborn, Joaquin Piriz, John Y. Lin, Sadegh Nabavi
bioRxiv 2021.05.05.442824; doi: https://doi.org/10.1101/2021.05.05.442824
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Dual-color optical activation and suppression of neurons with high temporal precision
Noëmie Mermet-Joret, Andrea Moreno, Agnieszka Zbela, Bárður Eyjólfsson Ellendersen, Nathalie Krauth, Anne von Philipsborn, Joaquin Piriz, John Y. Lin, Sadegh Nabavi
bioRxiv 2021.05.05.442824; doi: https://doi.org/10.1101/2021.05.05.442824

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