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.
Neuronal firing modulation by a membrane-targeted photoswitch / Difrancesco, M. L.; Lodola, F.; Colombo, E.; Maragliano, L.; Bramini, M.; Paterno, G. M.; Baldelli, P.; Serra, M. D.; Lunelli, L.; Marchioretto, M.; Grasselli, G.; Cimo, S.; Colella, L.; Fazzi, D.; Ortica, F.; Vurro, V.; Eleftheriou, C. G.; Shmal, D.; Maya-Vetencourt, J. F.; Bertarelli, C.; Lanzani, G.; Benfenati, F.. - In: NATURE NANOTECHNOLOGY. - ISSN 1748-3387. - (2020). [10.1038/s41565-019-0632-6]
Neuronal firing modulation by a membrane-targeted photoswitch
Maragliano L.;
2020-01-01
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.