Genetic and neural behavioural influences on social space in Drosophila melanogaster

Social behaviour is defined as a behavioural response of individuals to conspecifics and is necessary for species communication. Social interactions involve the perception, integration, and response to other individuals in a group and are facilitated by sensory integration in the brain, with specific synaptic signaling and neural circuitry leading to a behavioural output. In this thesis, I use Drosophila melanogaster to investigate the genetic and neural mechanisms underlying social space determination. Previous research has shown that social spacing in Drosophila can be influenced by intrinsic and extrinsic factors such as mating status, genetic mutations, and environmental conditions. One of the genetic factors includes orthologs of candidate genes for autism spectrum disorders such as the neuroligins. In this thesis, I focus specifically on the role of Neuroligin 3 (Nlg3), a transsynaptic membrane protein, and the associated adult fly brain structures in modulating social space determination. Using a combination of behavioural assays (social space and climbing assays), the Drosophila genetic toolkit, and immunocytochemistry, I examined the genetic and neural basis of nlg3 influencing social spacing. My results indicate that nlg3 influences social space in a sexually dimorphic manner, where male deficiency mutants displayed increased social space, while females showed an age-dependent effect. I also localized Nlg3 protein to the mushroom bodies, optic lobes, and protocerebral bridge. Knocking down nlg3 only in the optic lobes increased male social space, highlighting the importance of vision on the behaviour. However, the reduction of acetylcholine release from the mushroom bodies decreased female social space specifically. Modulation of fruitless-expressing neurons also has a sex-specific effect on social space, where again acetylcholine and GABA specifically decreased female social space but do not affect males. Overall, my work provides insights into the neural circuitry of social space in Drosophila and characterizes the effects of nlg3, emphasizing the broader significance of neuroligins in the context of social behaviour regulation. Better understanding of these pathways provides insight into potential targets of neuropsychiatric disorders such as autism, where social interactions are often impaired.