A photoswitch for modulating neuronal activity

DiFrancesco, M. L. et al. Nat. Nanotechnol. (2020).

A wide variety of azobenzene-based photoswitches have been developed for manipulating the activity of, for example, enzymes or receptors. Photoswitching involves the light-dependent transcis isomerization of the azobenzene moiety of the photoswitch molecule. The resulting conformational change modulates the activity of the target protein, molecule or structure. DiFrancesco et al. developed a photoswitch, called Ziapin2, that modulates membrane properties in response to blue light. Ziapin2, with amphiphilic properties, readily integrates into cell membranes, with a preference for lipid rafts. In the dark, Ziapin2 in the trans configuration leads to thinning of the membrane, which increases membrane capacitance. Upon illumination, membranes revert to their original state and hyperpolarize, which is followed by a rebound depolarization. When Ziapin2 is used in neurons, illumination elicits action potentials. DiFrancesco et al. demonstrate that Ziapin2 can be applied in vivo, where they elicit activity in the mouse somatosensory cortex upon loading with Ziapin2 and illumination.

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Correspondence to Nina Vogt.

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Vogt, N. A photoswitch for modulating neuronal activity. Nat Methods 17, 364 (2020).

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