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. Shen, Y., Ge, W. P., Li, Y., Hirano, A., Lee, H. Y., Rohlmann, A., ... & 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.
2. Liang, L., Li, Y., Potter, C. J., Yizhar, O., Deisseroth, K., Tsien, R. W., & Luo, L. (2013). GABAergic Projection Neurons RouteSelective Olfactory Inputs to Specific Higher-Order Neurons. Neuron, 79(5), 917-31.
3. Li Y*, and Tsien RW*. (2012) pHTomato, a red, genetically-encoded indicator that enables multiplex interrogation of synaptic activity.Nature Neuroscience. 15(7):1047-53.
4. Park H, Li Y and Tsien RW*. (2012) Influence of synaptic vesicle position on release probability and exocytotic fusion mode. Science.335(6074):1362-6.
5. Zhang Q, Li Y, and Tsien RW*. (2009) The dynamic control of kiss-and-run and vesicular reuse probed with single nanoparticles.Science. 323(5920):1448-53.
6. Kuner T*, Li Y, Gee K, Bonewald L, and Augustine G. (2008) Photolysis of a caged peptide reveals rapid action of N-ethylmaleimide sensitive factor before neurotransmitter release. Proc Natl Acad Sci U S A. 105(1):347-52.
7. Li Y, Augustine G, and Weninger K*. (2007) Kinetics of complexin binding to the SNARE complex: correcting single molecule FRET measurements for hidden events. Biophys J. 93(6):2178-87.