The overall objective of the proposed research is to elucidate the cellular and molecular mechanisms of toxicity from developmental exposure to harmful algal bloom (HAB) toxins. The HAB toxins domoic acid (DA), saxitoxin (STX), and anatoxin-a (ATX-a) occur in marine and coastal water bodies as well as in food sources and pose a significant threat to public health. Current regulatory guidelines for HAB toxins in seafood are designed to protect against acute exposure to adults. However, seafood with HAB toxins below the regulatory limits is regularly harvested and the consequences of exposure to low levels of HAB toxins particularly to children and young adults are not well understood. It is well known that the early life environment can profoundly influence health throughout the life course (the developmental origins of health and disease concept). The central hypothesis of the proposed research is that exposure to HAB toxins during early development alters various neuronal and glial cell types independently, leading to cell-type specific transcriptional changes, ultimately contributing to altered neurobehavioral outcomes. We propose to test this hypothesis using two complementary model systems: zebrafish, an established model organism for characterizing molecular, cellular, and behavioral changes in vivo, and human iPSC-derived 3D brain systems in vitro for elucidating the effects of toxins on differentiating human neural cells. In Aim 1, we will use transgenic zebrafish embryos and single-cell RNA sequencing to investigate the cellular and molecular mechanisms underlying the neurodevelopmental toxicity of DA, STX, and ATX-a. Building on our previous studies, in Aim 1.1 we will test the hypothesis that DA exposure of zebrafish embryos affects oligodendrocyte-neuron interactions in part by targeting oligodendrocytes that are necessary for the maturation and survival of axons. In Aim 1.2, we will test the hypothesis that STX exposure during developme