Neurobiology, molecular and cellular neurobiology and neuronal imaging
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.
1. #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.
2. #Zhou, M., #Chen, N., Tian, J., Zeng, J., ... Li, Y., *Guo, A., & *Li, Y. (2018). Suppression of GABAergic neurons through D2-like receptor secures efficient conditioning in Drosophila aversive olfactory learning. (2019). PNAS, 201812342.
3. Wu, L., Dong, A., Dong, L., Wang, S. Q., & *Li, Y. (2018). PARIS, an optogenetic method for functionally mapping gap junctions. eLife, 8, e43366.
4. 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.
5. 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.
6. #Sun, F., #Zeng, J., #Jing, M., Zhou, J., Feng, J., Owen, S., ... & *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.
7. #Jing, M., #Zhang, P., Wang, G., Feng, J., Mesik, L., Zeng, J., ... *Zhu, JJ & *Li, Y. (2018). A genetically-encoded fluorescent acetylcholine indicator for in vitro and in vivo studies. Nature Biotechnology, 36(8), 726-737.
8. #Chen, B., #Huang, X., Gou, D., Zeng, J., ... & Li, Y., *Chen, L., *Wang, A. (2018). Rapid volumetric imaging with Bessel-Beam three-photon microscopy. Biomedical optics express, 9(4), 1992-2000.
9. Shen, Y., Ge, W. P., Li, Y., Hirano, A., Lee, H. Y., Rohlmann, A., ... *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.
10. 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.
11. *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.
12. 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.
13. *Yoo, A. S., Sun, A. X., Li, L., Shcheglovitov, A., Portmann, T., Li, Y., ... & *Crabtree, G. R. (2011). MicroRNA-mediated conversion of human fibroblasts to neurons. Nature, 476(7359), 228-231.
14. 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.
15. *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.
16. 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：
1. *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.
2. 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.
3. #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.
4. Qian, C., & *Li, Y. (2015). Spine maturation and pruning during development: Cadherin/Catenin complexes come to help. Science China. Life sciences,58(9), 929.
5. *Li, Y., & *Rao, Y. (2015). Pied Piper of Neuroscience. Cell, 163(2), 267-268.