γ-Secretase plays a pivotal role in the central nervous system. Our recent development of genetically encoded Förster resonance energy transfer (FRET)-based biosensors has enabled the spatiotemporal recording of γ-secretase activity on a cell-by-cell basis in live neurons in culture. Nevertheless, how γ-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 γ-secretase activity in individual neurons in living mouse brains. Intriguingly, we uncovered that γ-secretase activity may influence the activity of γ-secretase in neighboring neurons, suggesting a potential ‘cell non-autonomous’ regulation of γ-secretase in mouse brains. Given that γ-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 γ-secretase in normal health and diseases.

Sensory signals from the body’s visceral organs (e.g. the heart) can robustly influence the perception of exteroceptive sensations. This interoceptive–exteroceptive interaction has been argued to underlie self-awareness by situating one’s perceptual awareness of exteroceptive stimuli in the context of one’s internal state, but studies probing cardiac influences on visual awareness have yielded conflicting findings. In this study, we presented separate grating stimuli to each of subjects’ eyes as in a classic binocular rivalry paradigm – measuring the duration for which each stimulus dominates in perception. However, we caused the gratings to ‘pulse’ at specific times relative to subjects’ real-time electrocardiogram, manipulating whether pulses occurred during cardiac systole, when baroreceptors signal to the brain that the heart has contracted, or in diastole when baroreceptors are silent. The influential ‘Baroreceptor Hypothesis’ predicts the effect of baroreceptive input on visual perception should be uniformly suppressive. In contrast, we observed that dominance durations increased for systole-entrained stimuli, inconsistent with the Baroreceptor Hypothesis. Furthermore, we show that this cardiac-dependent rivalry effect is preserved in subjects who are at-chance discriminating between systole-entrained and diastole-presented stimuli in a separate interoceptive awareness task, suggesting that our results are not dependent on conscious access to heartbeat sensations.