Recording gamma-secretase activity in living mouse brains
{gamma}-Secretase plays a pivotal role in the central nervous system. Our recent development of genetically encoded Forster resonance energy transfer (FRET)-based biosensors has enabled the spatiotemporal recording of gamma-secretase activity on a cell-by-cell basis in live neurons in culture. Nevertheless, how {gamma}-secretase activity is regulated in vivo remains unclear. Here we employ the near-infrared (NIR) C99 720-670 biosensor and NIR confocal microscopy to quantitatively record gamma-secretase activity in individual neurons in living mouse brains. Intriguingly, we uncovered that gamma-secretase activity may influence the activity of gamma-secretase in neighboring neurons, suggesting a potential "cell non-autonomous" regulation of gamma-secretase in mouse brains. Given that gamma-secretase plays critical roles in important biological events and various diseases, our new assay in vivo would become a new platform that enables dissecting the essential roles of gamma-secretase in normal health and diseases.