Subsequent effects of manipulating embryonic neuronal activity

这一提议将检验这样一种假设，即早期胚胎暴露于可能影响神经元信号的化合物中，将导致成人出现学习和/或行为问题。它的三个具体目的是：1)研究通过乙酰胆碱途径的异位信号如何导致最终影响成人学习/行为的变化；2)测试甘氨酸和GABA信号通路的信号干扰是否影响成人的学习/行为，并检查施加的分子/发育变化；3)评估可能影响神经元信号传导的环境化学物质对整个胚胎的影响。它对人类健康的潜在价值与大量化学物质有关，这些化学物质已经和正在被引入我们的环境，而没有进行足够的儿科或胚胎神经学检查。我们之前发现，很早就将斑马鱼胚胎暴露于毒死蜱会导致成年斑马鱼出现学习缺陷。在本提案中，我们计划检查受此挑战影响的早期事件，并挑战其他神经递质途径来测试假设的普遍性。所使用的技术将包括行为分析、创建和使用一些荧光转基因报告系、微阵列分析和高效液相色谱分析神经递质水平。

This proposal will be testing the hypothesis that exposure of the very early embryo to compounds that can impact upon neuronal signaling will result in adults with learning and or behavioral problems. Its three specific aims are: 1) to examine how ectopic signaling through the acetylcholine pathway results in changes that eventually influence adult learning/behavior; 2) to test whether signaling interference in the glycine and GABA pathways impact upon adult learning/behavior and to examine the molecular/developmental changes imposed and 3) to evaluate whole embryo effects of environmental chemicals that might affect neuronal signaling. Its potential value to human health is related to the large number of chemicals that have been and are being introduced into our environment without an adequate amount of pediatric or embryonic neurological examination. We have previously found that very early exposure of the zebrafish embryo to chlorpyrifos results in adults with learning deficiencies. In this proposal we plan to examine the early events affected by this challenge and to challenge other neurotransmitter pathways to test the generality of the hypothesis. The technologies used will include behavioral analyses, the creation and use of a number of fluorescent transgenic reporter lines to fish, microarray analysis, and HPLC analysis of neurotransmitter levels.