Principal Investigator

Yulong Li
Fluorescencent Probe, Neuroimaging, Synaptic Transmission, Signal Transduction, Neurological Diseases

phone: 62766905
address: School of Life Sciences Peking University Life Sciences Building,Mailbox 142, 5 Yi He Yuan Road Haidian, Beijing, China, 100871



Research Interests:

The human brain consists of billions of neurons, including thousands of cell types, connected to form networks by trillions of synapses. The interplay between distinct neuronal types through synapses by long range projections and short range local connections leads to cognitive brain functions such as perception, decision making and motor control. Neuromodulators control brain function by selectively recruiting or disengaging defined population of neurons through cell type-specific regulation of transmitter release, membrane excitability or both. The complex action of neuromodulators, the diversified neuronal cell types and the sophisticated anatomy of the brain together pose huge technical challenges for neuroscientists seeking to unravel the actions of neuromodulators within local circuitry. To overcome these problems, we are interested in developing a new palette of biosensors that can be used to visualize turnover of various neuromodulators. In addition, we are developing a novel genetically-encoded fluorescent detection platform that would enable the visualization of target activation by various neuromodulators in real time. Together, these efforts will not only yield new insights into the secretion and activation of neuromodulators with good spatial and temporal resolution, but also provide a novel fluorescent toolbox to the neuroscience community at large, enabling them to visualize their favorite neural circuit with cellular and synaptic specificity that is currently lacking.


Selected Publications:

Main Research Articles:

  1. Zhuo, Y.#, Luo, B.#, Yi, X., Dong, H., Miao, X., Wan, J., Williams, J. T., Campbell, M. G., Cai, R., Qian, T., Li, F., Weber, S. J., Wang, L., Li, B., Wei, Y., Li, G., Wang, H., Zheng, Y., Zhao, Y., Wolf, M. E., Zhu, Y., Watabe-Uchida, M., & Li, Y.* (2023). Improved green and red GRAB sensors for monitoring dopaminergic activity in vivo. Nature Methods
  2. Wang, H.#, Qian, T.#, Zhao, Y., Zhuo, Y., Wu, C., Osakada, T., Chen, P., Chen, Z., Ren, H., Yan, Y., Geng, L., Fu, S., Mei, L., Li, G., Wu, L., Jiang, Y., Qian, W., Zhang, L., Peng, W., Xu, M., Hu, J., Jiang, M., Chen, L., Tang, C., Zhu, Y., Lin, D., Zhou, J.-N., & Li, Y.* (2023). A tool kit of highly selective and sensitive genetically encoded neuropeptide sensors. Science
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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,
  12. 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,
  13. 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.
  14. 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.
  15. 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.
  16. Wu, L., Dong, A., Dong, L., Wang, S. Q., & Li, Y*. (2019). PARIS, an optogenetic method for functionally mapping gap junctions. eLife, 8, e43366.
  17. 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.
  18. 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.
  19. 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.
  20. 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.

Collaborative Publications:

  1. Sang, D.#, Lin, K.#, Yang, Y.#, Ran, G., Li, B., Chen, C., Li, Q., Ma, Y., Lu, L., Cui, X.-Y., Liu, Z., Lv, S.-Q., Luo, M., Liu, Q., Li, Y., & Zhang, E. E.* (2023). Prolonged sleep deprivation induces a cytokine-storm-like syndrome in mammals. Cell, 186(25), 5500-5516.e5521. 
  2. Terauchi, A., Yee, P., Johnson-Venkatesh, E. M., Seiglie, M. P., Kim, L., Pitino, J. C., Kritzer, E., Zhang, Q., Zhou, J., Li, Y., Ginty, D. D., Lee, W. A., & Umemori, H.# (2023). The projection-specific signals that establish functionally segregated dopaminergic synapses. Cell,
  3. Krok, A. C., Maltese, M., Mistry, P., Miao, X., Li, Y., & Tritsch, N. X.# (2023). Intrinsic dopamine and acetylcholine dynamics in the striatum of mice. Nature,
  4. Yu, X., Zhao, G., Wang, D., ...Li, Y., Dong, H.#, Franks, N.# & William, W. # (2022). A specific circuit in the midbrain detects stress and induces restorative sleep. Science, 377, 63-72.
  5. Provencher, V. #, Drummond, G., Feng, J., Li, Y. & Sur, M. # (2022). Spatiotemporal dynamics of noradrenaline during learned behavior. Nature, 606, 732-738.
  6. Liu, C. #, Cai, X., Ritzau-Jost, A., Kramer, P.F., Li, Y., Khaliq, Z.M., Hallermann, S. & Kaeser P.S. # (2022). An action potential initiation mechanism in distal axons for the control of dopamine release. Science, 375, 1378-1385.
  7. Hasegawa, E., Miyasaka, A., Sakurai, K., Cherasse, Y., Li, Y., & Sakurai, T. # (2022). Rapid eye movement sleep is initiated by basolateral amygdala dopamine signaling in mice. Science, 375(6584), pp.994-1000.
  8. Deng, H., Xiao, X., Yang, T., …, Li, Y., Huang, J. & Li, B. #. (2021) A genetically defined insula-brainstem circuit selectively controls motivational vigor. Cell, 184, 6344-6360.
  9. Wang, J.#, Li, J.#, Yang, Q.#, Xie, Y.-K., Wen, Y.-L., Xu, Z.-Z., Li, Y., Xu, T., Wu, Z.-Y., Duan, S., & Xu, H.* (2021). Basal forebrain mediates prosocial behavior via disinhibition of midbrain dopamine neurons. Proceedings of the National Academy of Sciences,118(7), e2019295118.
  10. Kim, H. R.*, Malik, A. N., Mikhael, J. G., Bech, P., Tsutsui-Kimura, I., Sun, F., Zhang, Y., Li, Y., Watabe-Uchida, M., Gershman, S. J., & Uchida, N.* (2020). A Unified Framework for Dopamine Signals across Timescales. Cell,
  11. Peng, W.#, Wu, Z.#, Kun, S.#, Zhang, S., Li, Y. & Min, X.* (2020). Regulation of sleep homeostasis mediator adenosine by basal forebrain glutamatergic neurons. Science, 369, 1208.
  12. Mazzone, C.M., Liang-Guallpa, J.,Li, C., Wolcott, N. S., Boone, M. H., Southern, M., Kobzar, N. P., Salgado, I. A., Reddy, D. M., Sun, F., Zhang, Y., Li, Y., Cui, G. * & Krashes, M. J.* (2020). High-fat food biases hypothalamic and mesolimbic expression of consummatory drives. Nature Neuroscience,
  13. Lin, R., Liang, J., Wang, R., Yan, T., Zhou, Y., Liu, Y., Feng, Q., Sun, F.,, Li, Y., Li, A., Gong, H., & Luo, M.* (2020). The Raphe Dopamine System Controls the Expression of Incentive Memory. Neuron, 1420-19.
  14. Handler, A., Graham, T. G. M., Cohn, R., Morantte, I., Siliciano, A. F., Zeng J., Li, Y. & Ruta, V.* (2019). Distinct dopamine receptor pathways underlie the temporal sensitivity of associative learning. Cell, 178(1), 60-75.
  15. Li, B.#, Wong, C.#, Gao, S. M., Zhang, R., Sun, R., Li, Y., & *Song, Y. (2018). The retromer complex safeguards against neural progenitor-derived tumorigenesis by regulating Notch receptor trafficking. eLife, 7, e38181.
  16. Tanaka, M., Sun, F., Li, Y., & Mooney, R.* (2018). A mesocortical dopamine circuit enables the cultural transmission of vocal behaviour. Nature, 563(7729), 117-120.
  17. Shen, Y., Ge, W. P., Li, Y., Hirano, A., Lee, H. Y., Rohlmann, A., Missler, M., Tsien, R. W., Jan, L. Y., Fu, Y. H.* & Ptacek, L. J.* (2015). Protein mutated in paroxysmal dyskinesia interacts with the active zone protein RIM and suppresses synaptic vesicle exocytosis. Proceedings of the National Academy of Sciences, 112(10), 2935-2941.
  18. Liang, L., Li, Y., Potter, C. J., Yizhar, O., Deisseroth, K., Tsien, R. W., & Luo, L.* (2013). GABAergic Projection Neurons Route Selective Olfactory Inputs to Specific Higher-Order Neurons. Neuron, 79(5), 917-931.
  19. Park, H., Li, Y., & Tsien, R. W.* (2012). Influence of synaptic vesicle position on release probability and exocytotic fusion mode. Science, 335(6074), 1362-1366.
  20. Yoo, A. S.*, Sun, A. X., Li, L., Shcheglovitov, A., Portmann, T., Li, Y., Lee-Messer, C., Dolmetsch, R. E., Tsien R. W. & Crabtree, G. R.* (2011). MicroRNA-mediated conversion of human fibroblasts to neurons. Nature, 476(7359), 228-231.
  21. Zhang, Q., Li, Y., & Tsien, R. W.* (2009). The dynamic control of kiss-and-run and vesicular reuse probed with single nanoparticles. Science, 323(5920), 1448-1453.
  22. Kuner, T.*, Li, Y., Gee, K. R., Bonewald, L. F., & Augustine, G. J. (2008). Photolysis of a caged peptide reveals rapid action of N-ethylmaleimide sensitive factor before neurotransmitter release. Proceedings of the National Academy of Sciences, 105(1), 347-352.

Reviews, Book Reviews and Highlights:

  1. Qian, T., Wang, H., Xia, X., & Li, Y.# (2023) Current and emerging methods for probing neuropeptide transmission. Current Opinion in Neurobiology, 81, 102751.
  2. 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, 44:1.
  3. Wu, Z., Lin, D. & Li, Y. # (2022). Pushing the frontiers: tools for monitoring neurotransmitters and neuromodulators. Nature Reviews Neuroscience, 23, 257-274.
  4. Zhuo, Y. & Li, Y. # (2022). New imaging methods for monitoring dopaminergic neurotransmission. Sci China Life Sci, 65(4): 838-841.
  5. Q&A: Yulong Li. (2021). Neuron, 109(21), 3346-3348.
  6. Wu, Z. #, & Li, Y. # (2020). New frontiers in probing the dynamics of purinergic transmitters in vivo. Neuroscience research, 152, 35-43.
  7. Wan, J. & Li, Y.* (2020). Recent Advances in Detection Methods for Neurotransmitters. Chinese Journal of Analytical Chemistry, 48(3), 307-315. (In Chinese)
  8. Wu, Z.* & Li, Y.* (2020). New frontiers in probing the dynamics of purinergic transmitters in vivo. Neuroscience Research,
  9. Zeng, J., Sun, F., Wan, J., Feng, J. & Li, Y.* (2019). New optical methods for detecting monoamine neuromodulators. Current Opinion in Biomedical Engineering,
  10. Jing, M., Zhang, Y., Wang, H. & Li, Y.* (2019). GPCR‐based sensors for imaging neurochemicals with high sensitivity and specificity. Journal of Neurochemistry,
  11. 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.
  12. 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.
  13. 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.
  14. Qian, C., & Li, Y.* (2015). Spine maturation and pruning during development: Cadherin/Catenin complexes come to help. Science China. Life sciences,58(9), 929.
  15. Li, Y.*, & Rao, Y.* (2015). Pied Piper of Neuroscience. Cell, 163(2), 267-268.

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