Neuronal firing modulation by a membrane-targeted photoswitch
Neuronal firing modulation by a membrane-targeted photoswitch
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DOI：
10.1038/s41565-019-0632-6
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发表时间：
2020-02-03
影响因子：
38.3
通讯作者：
Benfenati, Fabio
中科院分区：
文献类型：
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作者：
DiFrancesco, Mattia Lorenzo;Lodola, Francesco;Benfenati, Fabio
光学技术允许在高时空分辨率下调制神经元活动，这在神经科学中正变得至关重要。在这方面，偶氮苯基光开关是很有前途的纳米级神经元光刺激工具。在这里，我们设计了一种光敏偶氮苯化合物（Ziapin2），它稳定地分裂到质膜上，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，在加载了这种化合物的神经元中，可见光的毫秒脉冲会诱导短暂的超极化，然后是延迟的去极化，从而触发动作电位放电。这些效应是持续的，可以在体内被激发长达7天，证明Ziapin2在毫秒时间尺度上调节膜电容的潜力，而不直接影响离子通道或局部温度。光敏感的偶氮苯化合物可以被设计成稳定地分割到质膜上，从而使其在黑暗中变薄，在光刺激下松弛。在神经元中，由此产生的膜电容的光依赖性变化诱导了瞬态超极化，随后是反弹去极化和动作电位放电。
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.Light-sensitive azobenzene compounds can be engineered to stably partition into the plasma membrane, thus causing its thinning in the dark and relaxation upon light stimulation. In neurons, the resulting light-dependent change in membrane capacitance induces a transient hyperpolarization followed by rebound depolarization and action potential firing.