Bayer China Academic Collaboration Award 2022 -Investigator Award，2023
The 1st Feng Foundation of Biomedical Research，2021
CIBR (Chinese Institute for Brain Research, Beijing) Scholar,2020
XPLORER PRIZE in Life Sciences, 2019
The National Science Fund for Distinguished Young Scholars, 2019
The 12th Tan Jiazhen Life Science Innovation Award, 2019
Zhang Xiangtong Neuroscience Young Scientist Award, 2019
Research was selected into the Top Ten Progress of Life Sciences in China, 2018
Research was selected into the Top Ten News of Medical Science and Technology in China, 2018
VCANBIO Award for Innovations and Breakthrough in Life Sciences and Medicine, 2018
PKU & Boehringer-Ingelheim Faculty Research Award, 2018
“Green Leaf Eminent Young Scholar” Fellowship, Luye Pharma Group Co.,Ltd， 2015

2023-present，Neuron，Advisory Board
2022-2024, Society for Neurosciences, Program Committee Member
2022-present，National Science Review, Editor
2019-present, Journal of Neurochemistry, Editor

The human brain consists of billions of neurons, which 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.
The biggest challenge to study brain is its complexity. Our lab’s research centers on “synapse”, the fundamental unit for the communication between brain cells, called neurons. We carry two layers of research: first, we develop cutting edge research tools, namely advanced imaging probes, to untangle the complexity of nervous system in space and in time; second, capitalizing on the advancement of research toolkits, we study the regulation of synaptic transmission, focusing on the modulation of presynaptic transmitter release in health (e.g. sleep) and in disease conditions (e.g. neurodegenerative disease).
Specifically, for tool development, we focus on:
1. Development of non-invasive systems for opto-genetic mapping of electric synapses, a basic connection type between neurons. The malfunction of electric synapses could lead to devastating diseases such as deaf, heart problems, epilepsy and brain tumors.
2. Development of genetically-encoded sensors for imaging neurotransmitters/modulators. Those transmitters or modulators are crucial mediators for chemical synaptic transmission, important for our perception, learning/memory and our emotion.
Taking advantage of the above imaging sensors and additional, our functional studies are concentrating on:
1. Combined 2-photon imaging and genetically-encoded probes, studying how high brain centers are controlled during perception (olfaction) or sleep using fly and mice as model systems.
2. Matching the above novel chemical transmitters/ modulators with their cognate receptors: deorphanization of orphan receptors.
3. Exploration, identification and characterization of potential novel small molecule transmitters by a combination of bioinformatics, analytical chemistry, biochemistry, physiology and imaging approaches.

Main research articles:
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. 10.1038/s41592-023-02100-w.

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, 382(6672), eabq8173.

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, https://doi.org/10.1038/s41593-021-00823-7.

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, https://doi.org/10.1038/s41592-020-00981-9.

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, https://doi.org/10.1038/s41592-020-0953-2.

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.

Collaborative publications

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.

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, https://doi.org/10.1016/j.cell.2023.07.023.

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, https://doi.org/10.1038/s41586-023-05995-9.

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.

Provencher, V. #, Drummond, G., Feng, J., Li, Y. & Sur, M. # (2022). Spatiotemporal dynamics of noradrenaline during learned behavior. Nature, 606, 732-738.

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.

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.

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.

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. https://doi.org/10.1073/pnas.2019295118.

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, https://doi.org/https://doi.org/10.1016/j.cell.2020.11.013.

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.

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, https://doi.org/10.1038/s41593-020-0684-9.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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
Qian, T., Wang, H., Xia, X., & Li, Y.# (2023) Current and emerging methods for probing neuropeptide transmission. Current Opinion in Neurobiology, 81, 102751.

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.

Wu, Z., Lin, D., & Li, Y.* (2022). Pushing the frontiers: tools for monitoring neurotransmitters and neuromodulators. Nature Reviews Neuroscience.

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. Semin Liver Dis41(03), 358-367.

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, https://doi.org/10.1016/j.neures.2020.01.008.

Zeng, J., Sun, F., Wan, J., Feng, J. & Li, Y.* (2019). New optical methods for detecting monoamine neuromodulators. Current Opinion in Biomedical Engineering, https://doi.org/10.1016/j.cobme.2019.09.010.

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.

Laboratory Introduction