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. - ELETTRONICO. - 15:4(2020), pp. 296-306. [10.1038/s41565-019-0632-6]
Neuronal firing modulation by a membrane-targeted photoswitch
Fazzi D.;
2020
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.
