The effect of early life stress on serotonin signalling-related gene expression in zebrafish

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This project will investigate the interaction between early life stress and serotonergic signalling on behaviour across the life-span. In particular it will study the hypothesis that developmental stress during critical periods results in changes in the balance of serotonin (5HT) signalling via 5HT1A and 5HT7 receptors, affecting brain development and behaviour in later life. The hypothesis is based on reports of abnormalities in 5HT signalling during brain development as risk factors for the development of autism, schizophrenia, anxiety and depression in humans. In animals, experimental manipulations of 5HT signalling during early development cause changes in the neuronal architecture and behavioural changes in later life. Furthermore, our preliminary data has shown that developmental stress significantly affects 5HT receptor expression in zebrafish.The main objectives of the project are: To study the effects of developmental stress or pharmacological activation of stress hormone receptors on the expression 5-HT signalling pathway genes To characterise the effects of developmental stress and stress hormone receptor activation on brain development and behaviour To explore whether pharmacological interventions targeting 5-HT signalling can mitigate the effects of developmental stress To investigate whether pharmacological disruption of serotonin signalling, especially via 5HT1A and 5HT7 receptors, can mimic the effects of developmental stress on brain development and behaviourZebrafish are an ideal model system for this project as fertilisation and development occur externally enabling easy manipulation of the environment. A combination of genetic (gene expression profiling, in situ hybridisation, immunocytochemistry), pharmacological (targeted activation or blocking of serotonin or stress receptor signalling pathways) and behavioural assays will be used to study the interactions between early life stress, serotonin signalling, brain development and behaviour.