National Academy of Sciences, Proceedings of the National Academy of Sciences, 27(116), p. 13680-13689, 2019
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Significance Two-photon fluorescent probes to image intracellular calcium and other biochemical processes have revolutionized cell biology. In neurobiology, 2-photon calcium indicators produce signals that indirectly reflect action potential firing in neurons deep in the brain, and have become essential to record and correlate large-scale neural activity at high spatiotemporal resolution. Here we show that 2-photon excitable, diffusible photoswitches allow the activation and deactivation of neurotransmitter receptors with higher subtype-specificity and spatial resolution compared with previous molecular tools, and combined with calcium indicators enables to both control and readout activity using 2-photon excitation. Specifically, we used a potent and selective antagonist to switch on/off at the micrometer scale the activity of mGlu 5 receptors expressed endogenously in neurons and astrocytes of intact brain tissue.