The role of dopaminergic signalling during larval zebrafish brain development: a tool for investigating the developmental basis of neuropsychiatric disorders

摘要

Neurodevelopment depends on intrinsic and extrinsic factors that influence the overall pattern of neurogenesis and neural circuit formation, which has a direct impact on behaviour. Defects in dopamine signalling and brain morphology at a relatively early age, and mutations in neurodevelopmental genes are strongly correlated with several neuropsychiatric disorders. This evidence supports the hypothesis of a neurodevelopmental origin of at least some forms of mental illness. Zebrafish (Danio rerio) has emerged as an important vertebrate model system in bio-medical research. The ease with which intrinsic and extrinsic factors can be altered during early development, the relatively conserved dopaminergic circuit organisation in the larval brain, and the emergence of simple sensorimo-tor behaviours very early in development are some of the appealing features that make this organism advantageous for developmental brain and behaviour research. Thus, examining the impact of altered dopamine signalling and disease related genetic aberrations during zebrafish development presents a unique opportunity to holistically analyse the in vivo biochemical, morphological and behavioural significance of altered dopamine signalling during a crucial period of development using a highly tractable vertebrate model organism. Ultimately, this information will shed new light on potential therapeutic targets for the treatment of schizophrenia and perhaps serve as a paradigm for investigating the neurodevelopmental origin of other psychiatric disorders.