光探针观测神经元相互通讯
人的大脑有超过几十亿个神经元。这些神经元分为上千个种类，并通过上千亿个突触相互联系。我们发展高效的可遗传编码的荧光分子探针，研究新的成像的方法，并结合两者研究神经元细胞水平上的信号转导，分析神经环路中细胞可兴奋性及突触传递调控的机制。我们还用发展的可视化方法探索在疾病模型中的神经系统环路上的可能的病变及机能障碍。高灵敏的光学成像技术可以提供重要的时空分辨率，多路观测可以同时对多个神经元成像，这些新的方法对于揭开大脑神经调质的特异性的细胞基础提供了有效的方法。我们希望我们新的技术发展能让更多的神经生物学家能用简单有效的方法分析神经局部环路中复杂的突触的活动，解析大脑精巧的结构与功能的关系。
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 typespecific regulation of transmitter release, membrane excitability or both. Conventional neuromodulators such as neuropeptide-Y and opiates may exert their prolong effect by only acting on G-protein coupled receptors (GPCRs). In contrast, small molecule modulators such as GABA and acetylcholine may additionally gate ionotropic receptors and therefore also exhibit fast actions. 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, I am interested in developing a new palette of biosensors that can be used to visualize turnover of various neuromodulators. In addition, I am 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.
代表性论文
1. *Yulong Li， *Richard W Tsien , pHTomato, a red, genetically encoded indicator that enables multiplex interrogation of synaptic activity , Nature Neuroscience , 2012 , 15(7):1047-53 , [Abstract] , [Full Text] , *共同通讯作者
2. Hyokeun Park, Yulong Li, Richard W. Tsien* , Influence of Synaptic Vesicle Position on Release Probability and Exocytotic Fusion Mode , Science , 2012 , 335(6074):1362-6 , [Abstract] , [Full Text]
3. Qi Zhang, Yulong Li, Richard W. Tsien* , The Dynamic Control of Kiss-And-Run and Vesicular Reuse Probed with Single Nanoparticles , science , 2009 , 335(6074):1362-6 , [Abstract] , [Full Text]
4. T. Kuner, Y. Li, K. R. Gee, L. F. Bonewald, and G. J. Augustine* , Photolysis of a caged peptide reveals rapid action of N-ethylmaleimide sensitive factor before neurotransmitter release , Proc Natl Acad Sci U S A , 2008 , 105(1):347-52 , [Abstract] , [Full Text]
5. Yulong Li, George J. Augustine, Keith Weninger* , Kinetics of complexin binding to the SNARE complex:correcting single molecule FRET measurements for hidden events , Biophys J. , 2007 , 93(6):2178-87 , [Abstract] , [Full Text] |
