Rationally designed azobenzene photoswitches for efficient two-photon neuronal excitation
Control of the activity of individual worm neurons by two photons stimulation using a new photoswitch. In the image, a neuron in the tail of the worm (enlarged square region) is specifically activated in response to stimulation with pulses of infrared light. Image by Montserrat Porta (UAB) and Aida Garrido (IBEC).
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.
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.
PubMed: 30796228. Doi: 10.1038/s41467-019-08796-9. Free PMC article
