Study on the mechanism of olfactory neurons in regulating circadian rhythm
The olfactory neural circuitry plays a crucial role in regulating circadian rhythms. Our data demonstrate that mutation of the olfactory receptor orco in Drosophila significantly reduces rhythmicity in aged flies. Through neuPrint+ analysis and RNA-seq, we revealed that SIFamide (SIFa) neurons—which are associated with locomotor regulation—are closely connected to the olfactory neural circuit, and that the expression of the SIFa neuropeptide receptor (SiFaR) is significantly downregulated in orco mutants. Genetic evidence further indicates that olfactory receptor neurons receive external environmental signals and relay this information to SIFa neurons, thereby modulating the expression pattern of the core clock gene Period (Per), which ultimately affects circadian behavior in aging flies. Notably, the lifespan extension observed in orco mutants is closely associated with reduced Per expression in the gut. In summary, this study reveals that orco-dependent expression of Per in both the brain and the gut collectively contributes to age-related changes in circadian rhythmic behavior. This research provides new insights and a theoretical foundation for studying the mechanisms of aging by uncovering the intrinsic connection between olfactory neural circuits and circadian rhythmic behavior during aging. Overall design: RNA-seq was performed on head tissues of wildtype (w1118) and orco2 mutant Drosophila at Day 3 and Day 40, respectively, and on intestinal tissues of wildtype (w1118), orco2, and per01 mutants at Day 40.