German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany; Neuroscience Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg - Bad Krozingen, Germany; Medical Center - University of Freiburg, Freiburg, Germany.
Neuron. 2017 Nov 1;96(3):572-603. doi: 10.1016/j.neuron.2017.09.047.
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.
利用光敏感、基因编码分子来研究细胞生理学的能力，已经深刻地改变了神经科学。现代光遗传学工具包包括荧光传感器，用于可视化活细胞中的信号事件，以及光遗传学执行器，能够操纵许多细胞活动。大多数光遗传学工具都没有针对特定的亚细胞隔室，但在整个细胞中都有有限的辨别力定位。因此，光遗传学的激活通常不能反映高度局域化的细胞内信号事件的上下文依赖性效应。需要亚细胞靶向来实现更特异的光遗传学读出和光操控。在这里，我们首先详细概述了现有的光遗传学工具，重点是光遗传学执行器。其次，我们回顾了将这些工具靶向特定亚细胞隔室的既定策略。最后，我们讨论了目前光遗传学中缺失的有用工具和靶向策略，并为新型的亚细胞光遗传学应用提供了建议。
