Context-Dependent Modulation of Social Spacing by Dopamine Receptors in the Drosophila melanogaster Mushroom Body

Abstract

Social behaviour takes many forms, yet the fundamental principles of social circuit function are thought to be evolutionarily conserved. Foundational behaviours that precede more complex interactions can reveal the mechanisms underlying these circuits. Social spacing, the regulation of preferred inter-individual distances, is one such behaviour and can be quantified in the genetically tractable model Drosophila melanogaster. Dopamine and the mushroom body (MB) region regulate spacing in Drosophila, and extensive dopaminergic signalling occurs within this structure, but receptor-level contributions remain unclear. This thesis examines how the four dopamine receptors (DopEcR, Dop1R1, Dop1R2, Dop2R) mediate MB-targeted dopaminergic signalling during spacing. Manipulating receptor expression in the entire MB or specific lobes revealed spacing effects that depended on receptor identity, sex, lobe, and genetic background. 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.

Summary for Lay Audience

Social behaviour is a fundamental part of life across the animal kingdom. These behaviours can take many forms, but they all rely on a common process: communication within the brain. Networks of neurons work together to detect social cues, interpret them, and guide appropriate responses. Although social behaviours look different across species, the basic neural circuits that support them are thought to be evolutionarily conserved. Studying these circuits deepens our understanding of social behaviour and may also help explain why social functioning can become disrupted in various neuropsychiatric disorders. One way to study social behaviour is to focus on simple, foundational social actions that precede more complex interactions. A clear example of this is social spacing, which refers to how individuals choose to position themselves in relation to others to maintain comfortable distances. Humans adjust their “personal space” constantly, and many animals do the same, including the vinegar fly Drosophila melanogaster. These flies are a nuisance in the kitchen, but an asset in the lab: they can be genetically modified, and their spacing behaviour can be measured with precision. Two regulators of social spacing in Drosophila are the neurotransmitter dopamine and a brain region called the mushroom body (MB), a learning-related structure that shares functional similarities with the mammalian hippocampus. Dopamine acts as a messenger between neurons, including those in the MB. To receive this signal, MB neurons use dopamine receptors, but the roles of these receptors in social spacing are unclear. This thesis examined how altering expression of four dopamine receptors in the Drosophila mushroom body impacted social spacing. Effects varied depending on the receptor studied, the sex of the fly, the region of the MB examined, and the fly’s genetic background, showing that each receptor’s contribution is context-dependent. These findings support a model in which all four receptors help flies decide how close or far to stand from others and suggest that this circuit can be tuned differently depending on biological and genetic context. Since both dopamine and social circuits are conserved, this work may offer insight into how the brain regulates social behaviour in other species.

Description

Keywords

Dopamine, Dopamine receptor, Drosophila melanogaster, Genetic background, Mushroom body, Neural circuitry, Sexual dimorphism, Social behaviour, Social space

DOI

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