Social experience dependent modification of gene regulation and circuit function

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SUMMARY: Animals modulate their behaviors with social experience to increase fitness. The molecular and neural circuit-based mechanisms underlying social experience-dependent behavioral modulation remains unclear. Emerging evidence indicates the intimate connection among sensory experience, chromatin and behavioral modifications. Defects in chromatin modulation are associated with many neuropsychiatric disorders. Understanding the role of chromatin in regulating behaviors requires model systems with identified genes and neural circuits with clear causal links to stereotyped behaviors. The Drosophila melanogaster is an excellent model where these links were well elucidated for courtship behaviors. In D. melanogaster, Fruitless (Fru) and Doublesex (Dsx) are master transcriptional regulators that control innate and learned sex-specific courtship behaviors, respectively. fru is expressed in 2000 interconnected neurons marking courtship circuits. Socially isolated wild type males show elevated courtship compared to grouped males. Conversely, socially isolated fruM mutant males do not court, however, if grouped, they use olfaction to learn to court either males or females. This learning requires the gene dsx, which is co-expressed with fru in decision-making neurons of courtship circuits. How social experience regulates fru and dsx expression in the courtship circuits to modify circuit function remains unknown. In published and preliminary data, we demonstrated that social experience and pheromone signaling induces chromatin-based reprogramming of fru and dsx expression in the peripheral and central courtship circuits. We also found that social cues change Fru target neuromodulatory gene expression in the peripheral neurons, which alter neuronal sensitivity and circuit function. We hypothesize that detection of social signals reprograms chromatin around behavioral switch genes such as Fru and Dsx in the central brain, which in turn modulate circuit function and behaviors. To test this, we propose to identify social experience and pheromone signaling-dependent changes in chromatin around fru and dsx genes, their effects on downstream target gene expression, circuit function and behavioral outputs.