TY - JOUR
T1 - Rationally designed azobenzene photoswitches for efficient two-photon neuronal excitation
AU - Cabre, G.
AU - Garrido-Charles, A.
AU - Moreno, M.
AU - Bosch, M.
AU - Porta-de-la-Riva, M.
AU - Krieg, M.
AU - Gascon-Moya, M.
AU - Camarero, N.
AU - Gelabert, R.
AU - Lluch, J.-M.
AU - Busque, F.
AU - Hernando, J.
AU - Gorostiza, P.
AU - Alibes, R.
PY - 2019/2/22
Y1 - 2019/2/22
N2 - © 2019, The Author(s). 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.
AB - © 2019, The Author(s). 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.
KW - ABSORPTION
KW - ACTIVATION
KW - Animals
KW - Azo Compounds/chemistry
KW - Caenorhabditis elegans/physiology
KW - Calcium Channels/metabolism
KW - Cell Line
KW - Computational Biology/methods
KW - GLUTAMATE-RECEPTOR
KW - HEK293 Cells
KW - Humans
KW - Infrared Rays
KW - Neurons/metabolism
KW - OPTICAL CONTROL
KW - OPTOGENETICS
KW - PHOTOISOMERIZATION
KW - Patch-Clamp Techniques
KW - Photochemical Processes
KW - Photons
KW - REMOTE
KW - STIMULATION
UR - http://www.mendeley.com/research/rationally-designed-azobenzene-photoswitches-efficient-twophoton-neuronal-excitation
U2 - 10.1038/s41467-019-08796-9
DO - 10.1038/s41467-019-08796-9
M3 - Article
C2 - 30796228
SN - 2041-1723
VL - 10
SP - 907
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 907
ER -