Rationally designed azobenzene photoswitches for efficient two-photon neuronal excitation

Gisela Cabré, Aida Garrido-Charles, Miquel Moreno, Miquel Bosch, Montserrat Porta- de-la-Riva, Michael Krieg, Marta Gascón-Moya, Núria Camarero, Ricard Gelabert, José M. Lluch, Félix Busqué, Jordi Hernando, Pau Gorostiza () and Ramon Alibés ()
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Gisela Cabré: Universitat Autònoma de Barcelona (UAB)
Aida Garrido-Charles: Barcelona Institute of Science and Technology (BIST)
Miquel Moreno: Universitat Autònoma de Barcelona (UAB)
Miquel Bosch: Barcelona Institute of Science and Technology (BIST)
Montserrat Porta- de-la-Riva: The Barcelona Institute of Science and Technology (BIST)
Michael Krieg: The Barcelona Institute of Science and Technology (BIST)
Marta Gascón-Moya: Universitat Autònoma de Barcelona (UAB)
Núria Camarero: Barcelona Institute of Science and Technology (BIST)
Ricard Gelabert: Universitat Autònoma de Barcelona (UAB)
José M. Lluch: Universitat Autònoma de Barcelona (UAB)
Félix Busqué: Universitat Autònoma de Barcelona (UAB)
Jordi Hernando: Universitat Autònoma de Barcelona (UAB)
Pau Gorostiza: Barcelona Institute of Science and Technology (BIST)
Ramon Alibés: Universitat Autònoma de Barcelona (UAB)

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract Manipulation of neuronal activity using two-photon excitation of azobenzene photoswitches with near-infrared light has been recently demonstrated, but their practical use in neuronal tissue to photostimulate individual neurons with three-dimensional precision has been hampered by firstly, the low efficacy and reliability of NIR-induced azobenzene photoisomerization compared to one-photon excitation, and secondly, the short cis state lifetime of the two-photon responsive azo switches. Here we report the rational design based on theoretical calculations and the synthesis of azobenzene photoswitches endowed with both high two-photon absorption cross section and slow thermal back-isomerization. These compounds provide optimized and sustained two-photon neuronal stimulation both in light-scattering brain tissue and in Caenorhabditis elegans nematodes, displaying photoresponse intensities that are comparable to those achieved under one-photon excitation. This finding opens the way to use both genetically targeted and pharmacologically selective azobenzene photoswitches to dissect intact neuronal circuits in three dimensions.

Date: 2019
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DOI: 10.1038/s41467-019-08796-9

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