电压敏感染料成像因其较高的时空分辨率被广泛应用于非侵入式神经元电活动的介观水平研究，然而信号相对变化率低这一突出问题制约了成像效果。尽管可以开发性能优良的电压敏感的荧光蛋白，但是筛选工作的随机性较大。本项目以解决神经电位光学研究手段单一且荧光染料法信号响应弱的问题为目标，拟开展建立强信号响应的神经电位光学成像分析新方法的研究。通过信号转导的方法，借助等离子体共振能量转移作为信号转导杠杆，将电压敏感分子的局域光学吸收信号变化高效地转化为等离子体纳米颗粒散射信号的变化。进而通过高信号变化率的单颗粒光散射成像来指示电位变化，并最终用于介观水平的非侵入性神经电活动动态成像分析。通过本项目的研究，能达到开发新型膜电位单颗粒光学成像探针、同步记录神经元群体电活动和高通量考察药物神经毒性的目的，为神经系统疾病诊疗领域中处于基础地位的神经电生理研究提供实时成像分析新方法。

Voltage sensitive dye imaging (VSDI), as a non-invasive technology, has been widely applied to investigate the neuronal electrical activity at a mesoscopic level thanks to its high spatial and temporal resolution, however, an outstanding problem that the low relative ratio of change restricts the imaging efficiency. Although potential-sensitive fluorescent protein with high performance can be developed, there is a lot of randomness in the screening process. The aim of this program is to solve the existing problems, including the limited analysis methods for neuronal electrical activity determination and the aforementioned low relative ratio of change. Present program is to establish new method with high signal intensity to analyze the membrane potential in imaging mode. Plasmon resonance energy transfer is used as a leverage to accomplish the signal transduction from the light absorption signal of voltage sensitive molecule into the scattered light of plasmonic nanoparticles effectively. Then, the scattering imaging of single nanoparticle is used to probe the dynamic membrane potential. This program can develop new single nanoparticle optical probe of neuronal membrane potential, which can be used to record electrical activity of groups of neurons synchronously and achieve high throughput neurotoxicity study of drugs. Besides, this program can supply new optical imaging analysis methods for electrophysiology of nerve and diagnosis and treatment of nervous system disease.