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.

Two-photon absorption capacity of azobenzene photoswitches usually comes with a reduction in thermal stability. Here, the authors developed photoswitches with high two-photon sensitivity and enhanced cis isomer thermal lifetime for the control of glutamate receptors.

Details

Title
Rationally designed azobenzene photoswitches for efficient two-photon neuronal excitation
Author
Cabré Gisela 1 ; Garrido-Charles, Aida 2 ; Moreno, Miquel 1 ; Bosch Miquel 2 ; Porta-de-la-Riva, Montserrat 3 ; Krieg, Michael 3 ; Gascón-Moya, Marta 1 ; Camarero Núria 2 ; Gelabert Ricard 1 ; Lluch, José M 1   VIAFID ORCID Logo  ; Busqué Félix 1 ; Hernando Jordi 1 ; Gorostiza Pau 4   VIAFID ORCID Logo  ; Alibés Ramon 1   VIAFID ORCID Logo 

 Universitat Autònoma de Barcelona (UAB), Departament de Química, Cerdanyola del Vallès, Spain (GRID:grid.7080.f) 
 Barcelona Institute of Science and Technology (BIST), Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain (GRID:grid.473715.3) 
 The Barcelona Institute of Science and Technology (BIST), Institut de Ciències Fotòniques (ICFO), Barcelona, Spain (GRID:grid.473715.3) 
 Barcelona Institute of Science and Technology (BIST), Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain (GRID:grid.473715.3); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (GRID:grid.425902.8) (ISNI:0000 0000 9601 989X); Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain (GRID:grid.429738.3) (ISNI:0000 0004 1763 291X) 
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2185065107
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.