Cell: Li Yulong research group of Peking University has developed a new type of gene encoding dopamine fluorescence probe

Recently, the academic journal Cell published on-line a research paper entitled "agentially encoded flurescent sensor enables rapid and specific detection of dopamine in flights, fish, and mice" by Li Yulong research group of School of life sciences, Peking University Tsinghua joint center of life sciences and pku-idg / McGovern Institute of brain sciences In this study, Li Yulong research group developed a novel, gene encoded dopamine fluorescence probe and applied it to detect the dynamic changes of endogenous dopamine in Drosophila, zebrafish and mice The probe will be an important tool to study dopamine related neural circuits Dopamine is an important monoamine neurotransmitter In the central nervous system, a series of key neural functions, including learning, reward, attention and motion control, are regulated Dopamine imbalance in the brain can lead to mental illness or neurodegenerative diseases, such as ADHD, schizophrenia, Parkinson's disease, etc In addition, dopamine related neural circuits are also targets of addictive drugs such as cocaine In order to better study the role of dopamine in physiological and pathological processes, researchers need to detect the dopamine signal changes in specific brain regions in vivo in real time However, the existing detection methods can not meet the needs of researchers In order to solve this problem, Li Yulong research group has developed a gene encoded dopamine probe (grab DA), which embeds the fluorescent protein (cpegfp), which is sensitive to structural change, into human dopamine receptor, so that the chemical signal of dopamine can be converted into fluorescent signal Combining with the existing imaging technology, the dynamic change of dopamine concentration can be monitored in real time Li Yulong's team optimized the probe in an all-round way, so that it has high molecular specificity and space-time resolution In addition, they have developed two versions of probes with high / low affinity (named da1h and da1m respectively), which are suitable for different brain regions with different dopamine release Figure 1 Embedding fluorescent protein into dopamine receptor (source: cell) Figure 2 Da1h and da1m probe act on different brain regions (source: cell) because the probe has gene coding Li Yulong's research group expressed the probe in cells, mouse brain slices or in vivo Drosophila, zebrafish and mice by means of transfection, virus injection and construction of transgenic animals The results showed that the long-term expression of the probe had no significant effect on the growth of the model organism Using the probe, they detected dopamine release induced by electrical stimulation of mouse brain slices, and dopamine signal changes related to olfactory stimulation, visual stimulation, learning and memory, mating behavior in the brains of Drosophila, zebrafish and mice in vivo Li Yulong, researcher of School of life sciences, Peking University, is the corresponding author of this paper Sun Fangmiao, Zeng Jianzhi and Jing Miao, doctoral students of Li Yulong research group, are the co first authors; Feng Jiesi, Luo Yichen, Yong Zihao and Wang Huan have made important contributions to the research results The collaborators of this work include: Du Jiulin research group and Xu Min research group of Institute of neuroscience, Chinese Academy of Sciences; Zhang Siyu research group of Shanghai Jiaotong University; Cui Guohong research group of National Institutes of health of the United States; Lin Dayu research group of New York University; Anatol C kreitzer research group of San Francisco branch of University of California This work has been greatly supported by the State Key Laboratory of membrane biology, Peking University Tsinghua Life Science Joint Center, national key basic research and development plan (973 Plan), National Natural Science Foundation, young thousand talents plan and American brain plan.