研究方向：
人的大脑由数十亿的神经元组成，后者又通过数万亿的突触组成复杂的神经网络。不同种类的神经元经过或远或近的投射，通过突触与其他神经元进行信息交流，实现感知、决策和运动等高级神经功能。
研究大脑的最大挑战在于脑的高度复杂性。我们实验室集中在神经元通讯的基本结构突触上，从两个层面上开展研究：一是开发前沿的工具，即开发新型成像探针，用于在时间和空间尺度上解析神经系统的复杂功能；二是借助先进的工具探究突触传递的调节机制，特别是在生理及病理条件下对神经递质释放的调节。
具体而言，对于工具开发，我们集中于：
1，结合光遗传学和荧光成像，无损伤性的研究神经元之间的电突触连接。电突触的异常可导致耳聋、癫痫、脑部肿瘤和心脏功能异常等疾病。
2，开发可遗传编码的检测神经递质/调质的荧光探针。神经递质/调质是神经元化学突触传递的关键介导分子，与感知、学习和记忆以及情绪密切相关。
利用上述荧光探针，我们的功能性和生理性的研究集中于：
1，结合生物信息学、分析化学、生物化学、生理学和成像学方法，系统地探索和鉴定潜在的新型小分子神经递质。
2，研究神经元中重要的分泌性囊泡“高密度核心囊泡”的蛋白质组学，分析囊泡内的神经肽组成。这些神经肽对于调节食物摄取、侵犯性行为和生物节律有重要的调节作用。
3，寻找上述新型化学递质/调质小分子的对应受体，即寻找“孤儿”受体的配体。
4，结合双光子成像和可遗传编码的荧光探针，使用果蝇和小鼠作为模式生物，研究嗅觉传导或睡眠过程中脑的工作机制。
代表性科研论文：
Main Research Articles
· Wu, Z.#, Cui, Y.#, Wang, H.#, Wu, H., Wan, Y., Li, B., Wang, L., Pan, S., Peng, W., Dong, A., Yuan, Z., Jing, M., Xu, M., Luo, M.*, & Li, Y.* (2023). Neuronal activity-induced, equilibrative nucleoside transporter-dependent, somatodendritic adenosine release revealed by a GRAB sensor. Proceedings of the National Academy of Sciences, 120(14), e2212387120.
· Dong, H.#, Li, M.#, Yan, Y., Qian, T., Lin, Y., Ma, X., Vischer, H. F., Liu, C., Li, G., Wang, H., Leurs, R., & Li, Y.* (2023). Genetically encoded sensors for measuring histamine release both in vitro and in vivo. Neuron.
· Zeng, J.#*, Li, X.#, Zhang, R., Lv, M., Wang, Y., Tan, K., Xia, X., Wan, J., Jing, M., Zhang, X., Li, Y., Yang, Y., Wang, L., Chu, J., Li, Y., & Li, Y.*. (2023). Local 5-HT signaling bi-directionally regulates the coincidence time window for associative learning. Neuron.
· Qian, T.#, Wang, H.#, Wang, P.#, Geng, L., Mei, L., Osakada, T., Wang, L., Tang, Y., Kania, A., Grinevich, V., Stoop, R., Lin, D., Luo, M., & Li, Y.* (2023). A genetically encoded sensor measures temporal oxytocin release from different neuronal compartments. Nature Biotechnology.
· Wu, Z.*, He, K., Chen, Y., Li, H., Pan, S., Li, B., Liu, T., Wang, H., Du, J., Jing, M., & Li, Y.* (2021). A sensitive GRAB sensor for detecting extracellular ATP in vitro and in vivo. Neuron, 110(5), 770-782.e775.
· Dong, A., He, K., Dudok, B., Farrell, J. S., Guan, W., Liput, D. J., Puhl, H. L., Cai, R., Wang, H., Duan, J., Albarran, E., Ding, J., Lovinger, D. M., Li, B., Soltesz, I., & Li, Y.*. (2021). A fluorescent sensor for spatiotemporally resolved imaging of endocannabinoid dynamics in vivo. Nature Biotechnology.
· Wan, J., Peng, W., Li, X., Qian, T., Song, K., Zeng, J., Deng, F., Hao, S., Feng,J., Zhang, P., Zhang, Y., Zou, J., Pan, S., Shin, M., Venton, B. J., Zhu, J. J., Jing, M., Xu, M., Li, Y.*.(2021). A genetically encoded sensor for measuring serotonin dynamics. Nature neuroscience, 24(5), 746-752.
· Qian, C., Wu, Z., Sun, R., Yu, H., Zeng, J., Rao, Y., & Li, Y. * (2021). Localization, proteomics, and metabolite profiling reveal a putative vesicular transporter for UDP-glucose. eLife, 10, e65417.
· Sun, F.#, Zhou, J.#, Dai, B.#, Qian, T., Zeng, J., Li, X., Zhuo, Y., Zhang, Y., Wang, Y., Qian, C., Tan, K., Feng, J., Dong, H., Lin, D.*, Cui, G.*, & Li, Y.*.(2020). Next-generation GRAB sensors for monitoring dopaminergic activity in vivo. Nature methods, 17(11), 1156-1166.
· Jing, M.*, Li, Y., Zeng, J., Huang, P., Skirzewski, M., Kljakic, O., Peng, W., Qian, T., Tan, K., Wu, R., Zhang, S., Pan, S., Xu, M., Li, H., Saksida, L. M., Prado, V. F., Bussey, T., Prado, M. A. M., Chen, L., Cheng, H., Li, Y.*.(2020). An optimized acetylcholine sensor for monitoring in vivo cholinergic activity. Nature methods, 17(11), 1139-1146.
· Yu, H., Zhao, T., Liu, S., Wu, Q., Johnson, O., Wu, Z., Zhuang, Z., Shi, Y., He, R., Yang, Y., Sun, J., Wang, X., Xu, H., Zeng, Z., Lei, X., Luo, W.* & Li, Y.*. (2019). MRGPRX4 is a bile acid receptor for human cholestatic itch. eLife, 8, e48431.
· Feng, J., Zhang, C., Lischinsky, J. E., Jing, M., Zhou, J., Wang, H., Zhang, Y., Dong, A., Wu, Z., Wu, H., Chen, W., Zhang, P., Zou, J., Hires, S. A., Zhu, J. J., Cui, G., Lin, D., Du, J. & Li, Y.* (2019). A Genetically Encoded Fluorescent Sensor for Rapid and Specific In Vivo Detection of Norepinephrine. Neuron, 102(4), 745-761.
· Wu, Z.#, Feng, J.#, Jing, M., & Li, Y.* (2019). G protein-assisted optimization of GPCR-activation based (GRAB) sensors. Neural Imaging and Sensing 2019, vol. 10865, p. 108650N. International Society for Optics and Photonics.
· Wu, L., Dong, A., Dong, L., Wang, S. Q., & Li, Y*. (2019). PARIS, an optogenetic method for functionally mapping gap junctions. eLife, 8, e43366.
· Sun, F.#, Zeng, J.#, Jing, M.#, Zhou, J., Feng, J., Owen, S., Luo, Y., Li, F., Wang, H., Yamaguchi, T., Yong, Z., Gao, Y., Peng, W., Wang, L., Zhang, S., Du, J., Lin, D., Xu, M., Kreitzer, A. C., Cui, G. & Li, Y.* (2018). A genetically-encoded fluorescent sensor enables rapid and specific detection of dopamine in flies, fish, and mice. Cell, 174(2), 481-496.
· Jing, M.#, Zhang, P.#, Wang, G., Feng, J., Mesik, L., Zeng, J., Jiang, H., Wang, S., Looby, J. C., Guagliardo, N. A., Langma, L. W., Lu, J., Zuo, Y., Talmage, D. A., Role, L. W., Barrett, P. Q., Zhang, L. I., Luo, M., Song, Y., Zhu, JJ* & Li, Y*. (2018). A genetically-encoded fluorescent acetylcholine indicator for in vitro and in vivo studies. Nature Biotechnology, 36(8), 726-737.
· Li, Y.*, & Tsien, R. W.* (2012). pHTomato, a red, genetically encoded indicator that enables multiplex interrogation of synaptic activity. Nature neuroscience, 15(7), 1047-1053.
· Li, Y., Augustine, G. J., & Weninger, K.* (2007). Kinetics of complexin binding to the SNARE complex: correcting single molecule FRET measurements for hidden events. Biophysical journal, 93(6), 2178-2187.
Reviews, Book Reviews and Highlights
· Dong, C.#, Zheng, Y.#, Long-Iyer, K., Wright, E. C., Li, Y.*, & Tian, L.* (2022). Fluorescence imaging of neural activity, neurochemical dynamics, and drug-specific receptor conformation with genetically encoded sensors. Annual Review of Neuroscience, 45, 273-294.
· Wu, Z., Lin, D., & Li, Y.* (2022). Pushing the frontiers: tools for monitoring neurotransmitters and neuromodulators. Nature Reviews Neuroscience, 23(5), 257-274.
· Zhuo, Y., Li, Y.* (2022). New imaging methods for monitoring dopaminergic neurotransmission. Science China Life Sciences, 65.
· Yulong Li. (2021). Neuron, 109(21), 3346-3348.
· Yu, H., Wangensteen, K., Deng, T., Li, Y., & Luo, W.* (2021). MRGPRX4 in Cholestatic Pruritus. In Seminars in Liver Disease (Vol. 41, No. 03, pp. 358-367). Thieme Medical Publishers, Inc..
· Wan, J. & Li, Y.* (2020). Recent Advances in Detection Methods for Neurotransmitters. Chinese Journal of Analytical Chemistry, 48(3), 307-315. (In Chinese)
· Wu, Z.* & Li, Y.* (2020). New frontiers in probing the dynamics of purinergic transmitters in vivo. Neuroscience Research, 152, 35-43.
· Zeng, J., Sun, F., Wan, J., Feng, J. & Li, Y.* (2019). New optical methods for detecting monoamine neuromodulators. Current Opinion in Biomedical Engineering, 12, 68-74.
· Jing, M., Zhang, Y., Wang, H. & Li, Y.* (2019). GPCR‐based sensors for imaging neurochemicals with high sensitivity and specificity. Journal of Neurochemistry, https://doi.org/10.1111/jnc.14855.
· Dong, A.*, Liu, S., & Li, Y.* (2018). Gap Junctions in the Nervous System: Probing Functional Connections Using New Imaging Approaches. Frontiers in Cellular Neuroscience, 12, 320.
· Wang, H., Jing, M., & Li, Y.* (2018). Lighting up the brain: genetically encoded fluorescent sensors for imaging neurotransmitters and neuromodulators. Current Opinion in Neurobiology, 50, 171-178.
· Wang, A.#, Feng, J.#, Li, Y.*, & Zou, P.* (2018). Beyond Fluorescent Proteins: Hybrid and Bioluminescent Indicators for Imaging Neural Activities. ACS chemical neuroscience, 9(4), 639-650.
· Qian, C., & Li, Y.* (2015). Spine maturation and pruning during development: Cadherin/Catenin complexes come to help. Science China. Life sciences,58(9), 929.
· Li, Y.*, & Rao, Y.* (2015). Pied Piper of Neuroscience. Cell, 163(2), 267-268.
