Tunbak, Hande; (2022) Social Preference in Juvenile Zebrafish. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Social behaviours are essential for the survival and reproduction of many species, including our own. A fundamental feature of all social behaviour is social preference, which is an individual’s propensity to interact with members of their species (termed conspecifics). In an average population, various social preference behaviours are readily observed, ranging from uninterested (not engaging with conspecifics) to very social (engaging with conspecifics). Individuals expressing these behaviours are typically labelled as having an asocial or prosocial, respectively. Little is known about how the underlying social circuitry gives rise to such distinct social behaviours in the population. It is well established that adverse social experiences can impact social behaviour, including isolation during early development. Undesired social isolation (loneliness) alters behavioural patterns, neuroanatomy (e.g., brain volume) and neurochemistry in ways that resemble developmental neuropsychiatric disorders, including autism and schizophrenia. However, few studies have investigated the impact of early life isolation on social circuitry, and how this results in dysfunctional social behaviour commonly associated with these and other disorders. In this thesis, juvenile zebrafish was used to model social preference behaviour, as it is an excellent translational model for human developmental and behavioural disorders. Population-level analysis revealed that several features of social preference behaviour could be summarised via Visual Preference Index (VPI) scores representing sociality. Using multiple behavioural parameters, comprehensive investigations of asocial and prosocial fish identified via VPIs revealed distinct responses towards conspecifics between the two phenotypes. These initial results served as a baseline for facilitating the identification of atypical social behaviour following periods of social isolation. The impact of isolation on social preference was assessed by applying either the full isolation over the initial three weeks of development or partial isolation, 48 hours or 24 hours, before testing. Following periods of social isolation, juvenile zebrafish displayed anxiety-like behaviours. Furthermore, full and partial isolation of 48 hours, but not 24 hours, altered responses to conspecifics. To assess the impact of social isolation on the social circuitry, the brain activities of fish were analysed and compared between different rearing conditions using high-resolution two-photon imaging. Whole-brain functional maps of isolated social phenotypes were distinct from those in the average population. Isolation-induced activity changes were found mainly in brain regions linked to social behaviour, social cue processing, and anxiety/stress (e.g., the caudal hypothalamus and preoptic area). Since some of these affected regions are modulated by serotonin, the reversibility of the adverse effects of social isolation on preference behaviour was investigated by using pharmacological manipulation of the monoaminergic system. The administration of an anxiolytic the drug buspirone demonstrated that altered social preference behaviour in isolated fish could be rescued by acutely reducing serotonin levels. By investigating social preference at the behavioural and functional level in wild-type juvenile zebrafish, this work contributes to our understanding of how the social brain circuity produces diverse social preferences. Furthermore, it provides important information on how early-life environmental adversity gives rise to atypical social behaviour and the neurotransmitters modulating the circuit, offering new opportunities for effective intervention.

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