Despite recent advances in optogenetics, it remains challenging to manipulate gene expression in specific populations of neurons. We present a dual-protein switch system, Cal-Light, that translates neuronal-activity-mediated calcium signaling into gene expression in a light-dependent manner. In cultured neurons and brain slices, we show that Cal-Light drives expression of the reporter EGFP with high spatiotemporal resolution only in the presence of both blue light and calcium. Delivery of the Cal-Light components to the motor cortex of mice by viral vectors labels a subset of excitatory and inhibitory neurons related to learned lever-pressing behavior. By using Cal-Light to drive expression of the inhibitory receptor halorhodopsin (eNpHR), which responds to yellow light, we temporarily inhibit the lever-pressing behavior, confirming that the labeled neurons mediate the behavior. Thus, Cal-Light enables dissection of neural circuits underlying complex mammalian behaviors with high spatiotemporal precision.

中文翻译：

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钙和光控开关在激活的神经元中诱导基因表达。

尽管光遗传学最近有进展，但是在特定神经元群体中操纵基因表达仍然具有挑战性。我们提出了一种双蛋白开关系统，Cal-Light，它以光依赖的方式将神经元活性介导的钙信号转译为基因表达。在培养的神经元和脑切片中，我们显示Cal-Light仅在同时存在蓝光和钙的情况下以高时空分辨率驱动报告基因EGFP的表达。通过病毒载体将Cal-Light组分递送至小鼠的运动皮层，可标记与学习的压杆行为有关的兴奋性和抑制性神经元的子集。通过使用Cal-Light来驱动对黄光有反应的抑制性受体halhohodopsin（eNpHR）的表达，我们暂时抑制了操纵杆的按动行为，确认标记的神经元介导该行为。因此，Cal-Light能够以高时空精度解剖复杂的哺乳动物行为背后的神经回路。