环境低剂量重金属暴露所致学习记忆等神经行为功能改变是当前面临的主要健康问题，其机制不明确，尤其是多种金属共存时的毒作用及机制研究甚少，且主要重金属环境污染物Hg、Pb、Cd、As之间的联合作用尚未见研究报道。基于长期研究基础，结合本领域国内外有关最新研究和存在问题，提出环境Hg、Pb、Cd、As暴露可能通过Snk-SPAR途径引起突触稳态失调，导致学习记忆等神经行为功能障碍，且它们之间存在着联合作用的科学假设。拟采用正交试验设计，激光共聚焦、多导离子通道检测、细胞定量分析和siRNA、DNA重组等技术，在体内、体外，阐明Pb、Hg、Cd、As单独及其联合时，对突触稳态的影响并发现它们间可能存在的联合作用；同时，从反向和正向验证Snk-SPAR途径在重金属突触稳态调控中的作用，为深入研究重金属污染物的神经毒效应及作用机制，发现新的防治靶标提供新思路，为重金属污染的健康危险度评价提供科学依据。

The low dose of heavy metal exposure in survivable environment and the associated health risk of neurobehavioral function such as learning and memory are a topic of current debate and concern, and yet its mechanism is not clear, especially the toxic mode of action and mechanism of a variety of metal mixture, an environmental reality, very little studied. The study on the combinatorial effect of lead (Pb), mercury (Hg), cadmium (Cd) and arsenic (As), the major heavy metal environmental pollutants, has not been reported. Based on our long-term investigations and combined the latest researches and problems, the hypothesis is proposed that Hg, Pb, Cd, As exposure may be acting on Snk-SPAR pathway and lead to the disorder of synaptic homeostasis so cause the neurobehavioral dysfunction such as learning and memory impairment , moreover there is the joint action among the heavy metals. In this project, applying Confocal Laser Scanning Microscope, Patch Clamp Amplifier System and morphologic quantitative analysis, as well as cellular and molecular techniques of siRNA, DNA recombination and so on, we will try to elucidate the individual and combinatorial effects of Hg, Pb, Cd, As on synaptic homeostasis as well as discover joint action among them on integral, cellular and molecular level from experiments, while to test and verify the effect of Snk-SPAR pathway on regulation in synaptic homeostasis in the environment of heavy metals from reverse and forward. Our study will give additional information to reveal the neurotoxicity mechanism of heavy metal pollutants, provide new clues to discover the new target for heavy metal pollutants intoxication prevention and treatment and offer a scientific basis for further to their health risk assessment.