Cabre G, Garrido-Charles A, Moreno M, Bosch M, Porta-de-la-Riva M, Krieg M, Gascon-Moya M, Camarero N, Gelabert R, Lluch JM, Busque F, Hernando J, Gorostiza P, Alibes R.
Nat Commun 2019 Feb; 10: 907.
anipulation 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.
PubMed: 30796228. Doi: 10.1038/s41467-019-08796-9. Free PMC article