Abstract
© 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.
Original language | English |
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Article number | 907 |
Pages (from-to) | 907 |
Number of pages | 12 |
Journal | Nature Communications |
Volume | 10 |
Issue number | 1 |
DOIs | |
Publication status | Published - 22 Feb 2019 |
Keywords
- ABSORPTION
- ACTIVATION
- Animals
- Azo Compounds/chemistry
- Caenorhabditis elegans/physiology
- Calcium Channels/metabolism
- Cell Line
- Computational Biology/methods
- GLUTAMATE-RECEPTOR
- HEK293 Cells
- Humans
- Infrared Rays
- Neurons/metabolism
- OPTICAL CONTROL
- OPTOGENETICS
- PHOTOISOMERIZATION
- Patch-Clamp Techniques
- Photochemical Processes
- Photons
- REMOTE
- STIMULATION