Within a group, individuals establish their preferred distance from each other, or social space, a form of social behaviour. The resulting distance depends on the exchange of social cues from others that needs to be perceived and integrated within the organism’s neural circuitry. In humans, social spacing can be impaired in neuropsychiatric disorders such as autism and schizophrenia. When organisms are subject to social isolation, profound changes in social behaviour are observed in a variety of species from insects to mammals, including social space. However, the genetic and molecular mechanisms modulating a behavioural response to isolation and possible recovery remain to be elucidated. I first investigated the effects of social isolation and recovery on social space of Drosophila melanogaster. Then I studied the role of two potential modulators of social space in response to isolation: neuroligin3, an ortholog of the autism-relatedneuroligin genes, and dopamine, a neuromodulator. Manipulations of both neuroligin3 and dopamine affect social behaviour in many organisms, making them prime candidates to study their involvement in isolation and the recovery from isolation. Using a loss of function mutant, I determined that the neuroligin3 gene is required for a typical response to isolation, but protein levels remained unchanged after isolation. Using the fly Gal4-UAS system, I expressed RNAi against tyrosine hydroxylase in dopaminergic neurons to reduce dopamine levels. I found that dopamine was required for a response to isolation in a sex-specific manner and that dopamine levels decrease in males, but not females after isolation. To determine if neuroligin3 and dopamine are working together in modulating social space, I first assessed dopamine levels and found that they are reduced in the neuroligin3 mutant and without neuroligin3, dopamine levels did not change in response to social experience. Lastly, I conducted a small targeted genetic screen using RNAi against post-synaptic proteins at the synapse to begin identifying other candidates required for a response to isolation. This research identified neuroligin3 and dopamine in the modulation of Drosophila social space after isolation and recovery, and that role could potentially be conserved, as other basic molecular mechanisms first discovered in flies
