Neuronal firing modulation by a membranetargeted photoswitch DiFrancesco, Mattia Lorenzo Lodola, Francesco Colombo, ELisabetta Maragliano, Luca Bramini, Mattia Paternò, Giuseppe Maria Baldelli, Pietro Dalla Serra, Mauro Lunelli, Lorenzo Marchioretto, Marta Grasselli, Giorgio Cimò, Simone Colella, Letizia Fazzi, Daniele Ortica, Fausto Vurro, Vito Eleftheriou, Cyril Giles Shmal, Dmytro Maya-Vetencourt, José Fernando Bertarelli, Chiara Lanzani, Guglielmo Benfenati, Fabio Optical technologies allowing modulation of neuronal activity at high spatio-temporal resolution are becoming paramount in neuroscience. In this respect, azobenzene-based photoswitches are promising nanoscale tools for neuronal photostimulation. Here we engineered a light-sensitive azobenzene compound (Ziapin2) that stably partitions into the plasma membrane and causes its thinning through trans-dimerization in the dark, resulting in an increased membrane capacitance at steady state. We demonstrated that in neurons loaded with the compound, millisecond pulses of visible light induce a transient hyperpolarization followed by a delayed depolarization that triggers action potential firing. These effects are persistent and can be evoked in vivo up to 7 days, proving the potential of Ziapin2 for the modulation of membrane capacitance in the millisecond timescale, without directly affecting ion channels or local temperature. 2026-02-17T07:47:09Z 2026-02-17T07:47:09Z 2020-02-03 journal article Neuronal firing modulation by a membrane-targeted photoswitch ML DiFrancesco, F Lodola, E Colombo, L Maragliano, M Bramini, ... 2020, Nature Nanotechnology 15 (4), 296-306 https://hdl.handle.net/10481/111048 10.1038/s41565-019-0632-6 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Nature