Chemical exposures have been implicated as environmental risk factors that interact with genetic susceptibilities to influence individual risk for complex neurodevelopmental disorders, including autism spectrum disorder, schizophrenia, attention deficit hyperactivity disorder and intellectual disabilities. Altered patterns of neuronal connectivity represent a convergent mechanism of pathogenesis for these and other neurodevelopmental disorders, and growing evidence suggests that chemicals can interfere with specific signaling pathways that regulate the development of neuronal connections. There is, therefore, a growing interest in developing screening platforms to identify chemicals that alter neuronal connectivity. Cell-cell, cell-matrix interactions and systemic influences are known to be important in defining neuronal connectivity in the developing brain, thus, a systems-based model offers significant advantages over cell-based models for screening chemicals for effects on neuronal connectivity. The embryonic zebrafish represents a vertebrate model amenable to higher throughput chemical screening that has proven useful in characterizing conserved mechanisms of neurodevelopment. Moreover, the zebrafish is readily amenable to gene editing to integrate genetic susceptibilities. Although use of the zebrafish model in toxicity testing has increased in recent years, the diverse tools available for imaging structural differences in the developing zebrafish brain have not been widely applied to studies of the influence of gene by environment interactions on neuronal connectivity in the developing zebrafish brain. Here, we discuss tools available for imaging of neuronal connectivity in the developing zebrafish, review what has been published in this regard, and suggest a path forward for applying this information to developmental neurotoxicity testing.

化学暴露已被认为是与遗传易感性相互作用的环境危险因素，会影响个体对复杂神经发育障碍的风险，包括自闭症谱系障碍，精神分裂症，注意缺陷多动障碍和智力障碍。神经元连通性模式的改变代表了这些疾病和其他神经发育障碍的发病机理的趋同机制，越来越多的证据表明化学物质会干扰调节神经元连接发展的特定信号传导途径。因此，人们对开发筛选平台以识别改变神经元连接性的化学物质的兴趣与日俱增。单元格，已知细胞-基质相互作用和系统性影响对于定义发育中的大脑中的神经元连通性很重要，因此，基于系统的模型相对于基于细胞的模型提供了显着的优势，可用于筛选对神经元连通性有影响的化学物质。斑马鱼胚胎代表适合高通量化学筛选的脊椎动物模型，已证明可用于表征神经发育的保守机制。此外，斑马鱼容易接受基因编辑以整合遗传敏感性。尽管近年来在毒性测试中使用斑马鱼模型的情况有所增加，可用的多种工具来成像斑马鱼大脑中结构差异的方法尚未广泛应用于研究环境相互作用对基因的影响对斑马鱼大脑中神经元连通性的影响。在这里，我们讨论了可用于发展中的斑马鱼神经元连通性成像的工具，回顾了这方面已发表的内容，并提出了将这些信息应用于发育性神经毒性测试的途径。