Determining the impact of early adversity on the developing vertebrate brain

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PROJECT SUMMARY In humans, chronic stress in children and adolescents has long lasting and debilitating effects that persist well into adulthood. Victims of childhood trauma have increased susceptibility to develop anxiety disorders such as post-traumatic stress (PTSD), increased propensity to substance abuse, hyper-aggression, and, in some cases, psychiatric disorders such as schizophrenia. Despite the prevalence of childhood trauma, little is known about how early life adversity impacts the development and function of the brain. This proposal utilizes a novel model of early life adversity (ELA) in the developmental and molecular neurogenetic system, the zebrafish. We will examine the impacts of ELA on hormonal, neuronal and genetic factors underlying brain development, and study how they are altered by ELA. The study utilizes powerful tools and approaches established in zebrafish, including whole-brain imaging of neuroanatomy and neuronal activity, transgenic reporters of glucocorticoid singling, and genetic screening using CRISPR/Cas9 technology at multiple developmental time points. Because of the high homology of genes and neuronal circuits underlying stress between fish and humans, we expect the findings from this study to reveal critical insight into what biological effects childhood trauma has on the developing brain.