李毓龙, 研究员 - 北京大学IDG麦戈文脑科学研究所 (2023)

李毓龙, 研究员 - 北京大学IDG麦戈文脑科学研究所 (1)

研究兴趣:

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,实现感知觉、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。
2、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。
3、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。

代表性科研论文:

主要研究论文:

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.

合作发表论文:

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 Sciences118(7), e2019295118. https://doi.org/10.1073/pnas.2019295118

Song, Y., Xu, C., Liu, J., Li, Y., Wang, H., Shan, D., Wainer Irving, W., Hu, X., Zhang, Y.*, Woo Anthony, Y.-H.*, & Xiao, R.-P. Heterodimerization with 5-HT2BR Is Indispensable for β2AR-mediated Cardioprotection. Circulation Research, https://doi.org/10.1161/CIRCRESAHA.120.317011

Zhu, R.#, Zhang, G.#, Jing, M., Han, Y., Li, J., Zhao, J., Li, Y., & Chen, P. R.* (2021, 2021/01/25). Genetically encoded formaldehyde sensors inspired by a protein intra-helical crosslinking reaction. Nature Communications,12(1), 581. https://doi.org/10.1038/s41467-020-20754-4

Mayer, F. P., Iwamoto, H., Hahn, M. K., Grumbar, G. J., Stewart, A., Li, Y., & Blakely, R. D.* (2021). There`s no place like home? Return to the home cage triggers dopamine release in the mouse nucleus accumbens. Neurochemistry International, 142, 104894. https://doi.org/https://doi.org/10.1016/j.neuint.2020.104894

Bari*, A., Xu, S., Pignatelli, M., Takeuchi, D., Feng, J., Li, Y., & Tonegawa, S.* (2020). Differential attentional control mechanisms by two distinct noradrenergic coeruleo-frontal cortical pathways. Proceedings of the National Academy of Sciences, https://doi.org/10.1073/pnas.2015635117

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

Crouse,R. B., Kim, K., Batchelor, H. M., Kamaletdinova, R., Chan, J., Rajebhosale, P., Pittenger, S. T., Role, L. W., Talmage, D A., Jing, M. , Li, Y., Gao, X., Mineur , Y. S., & Picciotto, M. R. * (2020). Acetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances learning of cue-reward contingency. eLife, 9:e57335.

Kwak, H., Koh, W., Kim, S., Song, K., Shin, J., Lee, J. M., Lee, E. H., Bae, J. Y., Ha, G. E., Oh, J. Park, Y. M., Kim, S., Feng, J., Lee, S. E., Choi, J. W., Kim, K. H., Kim, Y. S., Woo, J., Lee, D., Son, T., Kwon, S. W., Park, K. D., Yoon, B. Lee, J., Li, Y. , Lee, H., Bae, Y. C., Lee, C. J.* & Cheong, E.* (2020). Astrocytes Control Sensory Acuity via Tonic Inhibition in the Thalamus. Neuron, https://doi.org/10.1016/j.neuron.2020.08.013.

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.

DeGroot, S.R., Zhao-Shea, R., Chung L., Klenowski, P.M., Sun, F., Molas, S., Gardner, P.D., Li, Y. & Tapper, A.R.* (2020). Midbrain dopamine controls anxiety-like behavior by engaging unique interpeduncular nucleus microcircuitry. Biological Psychiatry, https://doi.org/10.1016/j.biopsych.2020.06.018.

Zhu, P. K. ,Zheng, W. S. , Zhang, P., Jing, M., Borden, P. M., Ali, F., Guo, K., Feng, J., Marvin, J. S., Wang, Y., Wan, J., Gan, L., Kwan, A. C., Lin, L., Looger, L. L., Li, Y. & Zhang, Y.* (2020). Nanoscopic visualization of restricted nonvolume cholinergic and monoaminergic transmission with genetically encoded sensors. Nano Lett., https://doi.org/10.1021/acs.nanolett.9b04877.

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.

Zhang, X., Noyes, N. C. , Zeng, J., Li, Y. & Davis, R. L.* (2019). Aversive Training Induces Both Pre- and Postsynaptic Suppression in Drosophila. The Journal of Neuroscience, 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.

Liang, X., Ho, M. C., Zhang, Y., Li, Y., Wu, M. N., Holy, T. E., & Taghert, P. H.* (2019). Morning and Evening Circadian Pacemakers Independently Drive Premotor Centers via a Specific Dopamine Relay. Neuron, 102(4), 843-857.

Zhou, M.#, Chen, N.#, Tian, J., Zeng, J., Zhang, Y., Zhang, X., Guo, J., Sun, J., Li, Yulong., Guo, A.*, & Li, Yan.* (2019). Suppression of GABAergic neurons through D2-like receptor secures efficient conditioning in Drosophila aversive olfactory learning. PNAS, 201812342.

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.

Chen, B.#, Huang, X.#, Gou, D., Zeng, J., Chen , G., Pang, M., Hu, Y., Zhao, Z., Wu, H., Cheng, H., Zhang, Z., Xu, C., & Li, Y., Chen, L.*, Wang, A.* (2018). Rapid volumetric imaging with Bessel-Beam three-photon microscopy. Biomedical optics express, 9(4), 1992-2000.

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.

综述 & 书评:

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). GPCRbased 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.

实验室网站:

http://www.yulonglilab.org/

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