Exploring social fear and avoidance through biological and behavioural models of autism spectrum disorders and social anxiety

Abstract

Social anxiety disorder (SAD) is a common and debilitating disorder marked by excessive and persistent fear and avoidance of social situations in which individuals fear risk of negative evaluation and judgement. Social anxiety-like behaviour can be modelled in mice using behavioural tasks which produce behaviours homologous to some symptoms of the human disorder. One such task is the social fear conditioning (SFC) paradigm which pairs mild foot shock with interaction with novel, same-sex caged conspecifics. During fear extinction, mice are presented a series of novel social stimuli. Mice which spend increasingly more time investigating the social stimulus demonstrate social fear extinction, however others are resistant to fear extinction and persistently avoid social interaction.

The first experimental chapter of this thesis used the SFC task to explore genetic, developmental, and biological correlates of social anxiety-like behaviours in mice. As those with Fragile-X have substantially increased risk of SAD, we used a genetic animal model of the disorder, Fmr1 KO mice, to explore potential correlates of SAD.

In the second experimental chapter, we used the SFC paradigm to examine neural correlates for social fear and avoidance behaviours. We used fibre photometry, a temporally precise calcium imaging technique which allows for recording of neural activity in freely moving mice, together with the SFC task to examine which specific social approach and avoidance behaviours the dLS is associated with during fear extinction.

In the final experimental chapter, we used a chemogenetic approach to silence the dLS prior to social fear extinction to investigate if activity in the dLS played a causal role in behaviours associated with elevated dLS activity. Together the findings of this thesis not only advance our understanding of social anxiety-like behaviours but also hold promise for more targeted interventions and treatment strategies for individuals with SAD in the future.