Neuroligin 3 highlights sexually dimorphic circuitry in Drosophila social spacing

Abstract

In Drosophila melanogaster, the autism-related Neuroligin 3 (Nlg3) protein is a postsynaptic membrane protein important for synapse development and regulation, which plays a role in social spacing behaviour. Here, we report the localization of Nlg3 to the calyx of the mushroom bodies (MB), optic lobes (OL), and protocerebral bridge (PB). Using RNA interference, nlg3 knockdown in each of these structures recapitulated the effect of knocking down it in all nlg-3 neurons. Hyperactivation and silencing of these neurons in the MB, but not the PB, controls social space in males and females, while hyperactivating and silencing of all nlg3-expressing neurons, including within the MB, PB, and OL, regulates male and female social space. Knocking down neurotransmitter biosynthesis enzymes, which decreases the amount of neurotransmitter release, showed that reducing acetylcholine release from the MB decreased female social space, whereas knocking down any dopamine receptor in the MB increased male social space. Lastly, to investigate the sexually dimorphic effects on social spacing previously seen in nlg3 mutants, we examined a subset of sexually dimorphic fruitless-expressing (fru)P1 neurons known to regulate sexually dimorphic behaviours. Hyperactivation of those fruP1 neurons decreased social space in both sexes, while silencing those fruP1 neurons specifically increased male social space without affecting females. Our findings highlight a sex-specific social space neural circuitry that includes the OL, MB, and fruP1 neurons, while uncovering the underlying basis of some of the sex differences in this behaviour. Article SummaryIn vinegar flies (Drosophila melanogaster), the autism-related Neuroligin 3 protein (Nlg3) controls neuronal development and regulation but also affects fly social behaviour. Nlg3 is localized to the mushroom bodies (MB), protocerebral bridge, and the optic lobes. We show that those structures are important in determining social space in a sex dependant manner. In addition, reducing acetylcholine release from the MB affects female social space, while reducing dopamine receptors of the MB only affect male behaviour. Finally, the fruitless sexually dimorphic neurons control social behavior differently in males and females.