The ability to study cellular physiology using photosensitive, genetically encoded molecules has profoundly transformed neuroscience. The modern optogenetic toolbox includes fluorescent sensors to visualize signaling events in living cells and optogenetic actuators enabling manipulation of numerous cellular activities. Most optogenetic tools are not targeted to specific subcellular compartments but are localized with limited discrimination throughout the cell. Therefore, optogenetic activation often does not reflect context-dependent effects of highly localized intracellular signaling events. Subcellular targeting is required to achieve more specific optogenetic readouts and photomanipulation. Here we first provide a detailed overview of the available optogenetic tools with a focus on optogenetic actuators. Second, we review established strategies for targeting these tools to specific subcellular compartments. Finally, we discuss useful tools and targeting strategies that are currently missing from the optogenetics repertoire and provide suggestions for novel subcellular optogenetic applications.

中文翻译：

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用于神经科学中亚细胞应用的光遗传学工具。

使用光敏的，遗传编码的分子研究细胞生理的能力已深刻改变了神经科学。现代的光遗传学工具箱包括荧光传感器，用于可视化活细胞中的信号事件，以及光遗传学致动器，可操纵多种细胞活动。大多数光遗传学工具并不针对特定的亚细胞区室，而是在整个细胞内以有限的辨别力定位的。因此，光遗传学激活通常不反映高度定位的细胞内信号转导事件的上下文相关的影响。需要亚细胞靶向以实现更具体的光遗传学读数和光操纵。在这里，我们首先提供可用的光遗传学工具的详细概述，重点是光遗传致动器。第二，我们回顾了针对这些工具针对特定亚细胞区室的既定策略。最后，我们讨论了光遗传学资料库中目前缺少的有用工具和靶向策略，并为新型亚细胞光遗传学应用提供了建议。