Center for Synaptic Neuroscience, Istituto Italiano di Tecnologia, Genoa, Italy.
IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Nat Nanotechnol. 2020 Apr;15(4):296-306. doi: 10.1038/s41565-019-0632-6. Epub 2020 Feb 3.
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.
光学技术能够以高时空分辨率调节神经元活动，在神经科学领域变得至关重要。在这方面，基于偶氮苯的光开关是用于神经元光刺激的有前途的纳米级工具。在这里，我们设计了一种对光敏感的偶氮苯化合物（Ziapin2），它可以稳定地分配到质膜中，并在黑暗中通过反式二聚化使其变薄，从而在稳态下增加膜电容。我们证明，在负载有该化合物的神经元中，可见光的毫秒脉冲会引起短暂的超极化，随后是延迟的去极化，从而引发动作电位的发放。这些效应是持久的，可以在体内持续 7 天以上被激发，证明了 Ziapin2 有潜力在毫秒时间尺度上调节膜电容，而不会直接影响离子通道或局部温度。
