ABSTRACT
The ability to modulate the activity of signaling molecules or enzymes is key to investigating their contributions to molecular, cellular, and behavioral changes. Moving beyond the cellular level to in vivo studies necessitates the tools which become versatile and controllable without producing adverse effects. Opsin-free optogenetic tools have notable advantages given that their activities are controlled by light in a highly spatiotemporal manner. Jung et al. developed a non-invasive optogenetic Flp recombinase for manipulating gene expression in the mouse brain. The tool, consisting of the Lyn-cytosolic Fas domain-Cry2PHR-EGFP, exerted cell death signaling via blue light illumination in cultured HeLa cells. However, distinct signaling mechanisms were observed in hippocampal DG. Kim et al. demonstrated that Fas signaling could be photo-manipulated to promote adult neurogenesis and working memory enhancement in living rodents. The large packaging capacity of LV enables broader applications that require extensive optogenetic tools compared to AAVs.
