Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Doctor of Philosophy

Program

Biology

Supervisor

Simon, Anne F.

Abstract

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.

Summary for Lay Audience

The research presented in this thesis aims to understand the genetic and neural factors that influence social behaviour in Drosophila melanogaster, commonly known as vinegar flies. Social behaviour, such as deciding how close to be to others in a group setting, is vital for the survival and reproduction of many animals, including humans. In Drosophila, social space, the distance between flies in a group, can vary depending on intrinsic and extrinsic factors. Understanding what controls this behaviour in flies can provide insights into social behaviours in all other organisms, including humans.

I focused on a specific gene called neuroligin 3 (nlg3), which is involved in forming and maintaining connections between neurons. This gene has been linked to social behaviour in many animals, including humans, where changes in its function can lead to conditions like autism. Using Drosophila, this study characterizes how nlg3 influences fly social space. I found that a deletion of this gene causes male flies to be further apart in social space, while female flies only showed this effect as they aged. By identifying adult fly brain regions and specific neural circuits are both associated with nlg3 and influence social space, my study highlights that this gene plays a role in controlling fly social behaviour. Reducing Nlg3 levels in the optic lobes, the visual center of the fly brain, increases fly social space. However, a reduction of the neurotransmitter release from the mushroom bodies, the sensory integration and learning and memory center in the fly brain, increases fly social space.

These findings show how a single gene can have complex effects on Drosophila behaviour, influenced by factors such as sex and age. This research contributes to understanding the genetic basis of social behaviour and its implications for conditions like autism, suggesting that similar genetic mechanisms may regulate social interactions across species.

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