Social experience alters behaviors by reprogramming the Fruitless pathway and circadian state in Drosophila

Animals thrive with social interactions and suffer significant adverse mental and physical health consequences when isolated. From flies to humans, social experience affects various cognitive and behavioral processes. Here, we use the fruit flies to show that group housing suppresses male courtship vigor as a result of a decrease in the evoked neural responses in courtship circuits. Bulk tissue RNAseq and single-cell RNAseq from fru - and dsx -positive cells from grouped or isolated male brains revealed that social isolation increases the number of fru - and dsx -positive neurons, elevates fru transcript levels in specific clock neurons, and dsx transcript levels throughout the brain. Knocking down fru ^M in the fru -positive neurons in brains decreases courtship in isolated males to levels comparable to those of group-housed males. Furthermore, group housing increases the expression of sr and Hr38 genes encoding neural activity-induced transcription factors in most neurons within social circuits. We found that knocking down sr in fru positive neurons effectively eliminates the impact of social experience by increasing courtship in group-housed males. Importantly, social experience also alters the expression of Fru ^M /Dsx ^M target genes regulating circadian states throughout the brain. Disrupting circadian gene function also diminishes the effect of group housing on courtship. Our findings suggest that group housing/social enrichment suppress courtship by reprogramming the circadian arousal state, whereas courtship-elevating effects of social isolation rely on changes in Fru ^M expression and function. These results are significant as they point to modulation of circadian arousal state as a possible central strategy for mediating the pleiotropic effects of social experience on organismal responses.