The Effect of Social Experience on Gene Regulation, Neural Activity and Behavior of Drosophila melanogaster

Abstract

Social experience plays a crucial role in shaping behavior and neural function across species. In humans, social interactions influence cognition, emotional regulation, and mental health, while social deprivation can lead to stress, depression, and neurological disorders. Similarly, animals exhibit adaptive changes in behaviors such as sleep, aggression, and reproduction based on social context, driven by underlying shifts in gene regulation and neural activity. Despite substantial evidence linking social experience to molecular and neural plasticity, the mechanisms through which social interactions alter gene expression within neuronal circuits to drive behavioral changes remain poorly understood. Here, I use Drosophila melanogaster as a model and employ multi-omics techniques, courtship behavior assays, and imaging approaches to investigate how social experience modulates gene expression, neural activity, and behavior from the peripheral sensory system to the central brain. In the peripheral olfactory system, social isolation or disruption of pheromone receptors Or47b and Or67d, as well as the transcription factor Fruitless (Fru), results in significant changes to transcriptional programs involved in neural activity. Many Fru target genes involved in regulating membrane potential and synaptic transmission are misregulated in the same direction in fru and pheromone receptor mutants, revealing a gene regulatory cascade from pheromone detection to transcriptional remodeling via Fru function. In the central brain, social experience modulates the transcriptional profiling of fru and doublesex (dsx) circuits. fru and an immediate early gene stripe function in fru circuit to mediate social experience-dependent behavior changes. Additionally, circadian and sleep-related genes (Clock, timeless, and Salt-inducible kinase 3) contribute to the modulation of courtship behavior by social experience, indicating the integration of internal states with external social cues. Furthermore, disrupting social signal detection through mutations in transcription factors Fru and Dsx, and in olfactory receptors (Or47b, Or67d) partially normalizes social experience-dependent transcriptomic differences in the brain, highlighting their role in maintaining molecular plasticity in response to social experience. Moreover, dysfunction of these four genes influences transcriptomic and chromatin states of the brain, potentially contributing to the regulation of various biological processes, including immune responses, metabolism, and signal transduction. Together, these findings provide new insights into how social experience drives molecular and neural plasticity, laying a foundation for future research on the molecular mechanisms underlying the influence of social experience on behavior.