Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Doctor of Philosophy

Program

Biology

Supervisor

Simon, Anne F.

Abstract

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.

Summary for Lay Audience

Social behaviour is fundamental to the lives of humans and other organisms. For social behaviour to occur, organisms must interact with others which relies on the functioning of neural connections, or circuitry. Social behaviour can be affected when neural circuitry is unable to properly transmit information throughout the brain, like in individuals with neuropsychiatric disorders. One social behaviour shared between humans and other organisms is the determination of a personal bubble, referred to as social space. It is unknown how the functioning of neural circuitry affects social space. Social isolation causes changes in social behaviour in many animals and has detrimental psychological and health consequences in humans. How social isolation or the recovery from isolation affects the neural circuitry and alters social behaviour is unknown. Using the powerful genetics of the vinegar fly (commonly called a fruit fly), Drosophila melanogaster, I examined how social space is affected by isolation and looked for a potential recovery after resocialization. Flies were further apart from each other after isolation, but social space was recovered when flies had time to interact with others. I also examined two components of neurons that are important for social behaviour in many organisms: neuroligin, that in humans is found to be mutated in people with autism spectrum disorders, and a chemical in the brain called dopamine that both humans and flies share. I discovered that changes in social space in flies didn’t happen after isolation when the two components are either absent or reduced in males (but not females), indicating they may be involved in the functioning of the neural circuitry regulating social space. Dopamine levels in males decreased in the brain after isolation but were recovered. This research can give us insight into the components of neurons that drive social behaviour that are potentially shared between flies and other organisms including humans.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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