Context-dependent modulation of social space by dopamine receptors in the Drosophila melanogaster mushroom body

Social behavior takes many forms, yet the fundamental principles of social circuit function are thought to be evolutionarily conserved. Foundational behaviors that precede more complex interactions can reveal the mechanisms underlying these circuits. Social spacing, the regulation of preferred inter-individual distances, is one such behavior and can be quantified in the genetically tractable model Drosophila melanogaster. Dopamine and the mushroom body brain region regulate spacing in Drosophila, and extensive dopaminergic signaling occurs within this structure, but receptor-level contributions remain unclear. This report examines how the four dopamine receptors (DopEcR, Dop1R1, Dop1R2, Dop2R) mediate mushroom body-targeted dopaminergic signaling during spacing. Manipulating receptor expression in the entire mushroom body or specific lobes revealed spacing effects that depended on genetic background, receptor identity, sex, and lobe. Receptors could be organized into two opposing pairs: DopEcR and Dop1R1 manipulations increased inter-individual distance, whereas Dop1R2 and Dop2R manipulations decreased inter-individual distance. However, each receptor produced a distinct pattern of effects when male and female data were analyzed across all three mushroom body lobes. These findings support a model in which distributed dopaminergic input engages all four receptors to shape context-dependent spacing decisions, offering insight into social circuit organization in Drosophila and beyond.