1、神经突触与环路结构的高精度解析
大量神经元通过更多突触联结形成精细的神经环路是大脑高级功能的物质基础,其中的巨大复杂性是人们理解脑功能原理的关键挑战。我们试图通过多种生物物理技术包括传统电生理学技术和前沿超微成像技术的应用、发展和整合,以纳米分辨率解析突触联结的分子组织构架与功能状态,描述神经环路的精细联结图谱,长期目标是在此基础上刻画实现基本脑功能的神经线路图,为设计下一代类脑计算装置提供依据。
2、突触可塑性与神经网络动力学
可塑性包括峰时依赖的突触可塑性(STDP)以及稳态可塑性是神经突触的重要性质,突触的可塑性变化与神经元网络电活动相互作用,形成复杂而有序的动态系统。我们利用膜片钳、多电极记录、高速荧光成像以及光遗传学操作等手段,在离体培养的神经元模型体系中探索神经网络的回响活动等基本动力学特性,以及复杂(生理)条件下突触可塑性的规则和分子细胞机制,并结合行为药理学、免疫组织化学、病毒示踪等方法,在整体动物模型中研究学习记忆行为与疾病的神经突触可塑性与环路基础。
3、神经环路解析前沿技术
通过多学科交叉合作,我们特别关注解析神经突触与环路结构功能的有效技术与方法,重点发展与应用随机光学重构显微(STORM)、冷冻电镜成像(CryoEM)、光电关联成像等不同尺度的显微成像技术,并合作开发相应的荧光与靶向分子探针,同时,我们也在合作探索神经示踪病毒的跨突触传播机制和应用方法。
Li XY., Liu HJ., Sun XX., Bi GQ, Zhang GQ. (2013) Highly Fluorescent Dye-Aggregate- Enhanced Energy-Transfer Nanoparticles for Neuronal Cell Imaging. Adv Opti Mater 1(8):549-553.
Gerkin, RC, Nauen, DW, Xu, F & Bi, GQ. (2013) Homeostatic regulation of spontaneous and evoked synaptic transmission in two steps. Mol Brain 6, 38, doi:10.1186/1756-6606-6-38.
Shim, SH, Xia, C, Zhong, G, Babcock, HP, Vaughan, JC, Huang, B, Wang, X, Xu, C, Bi, GQ & Zhuang, X. (2012) Super-resolution fluorescence imaging of organelles in live cells with photoswitchable membrane probes. Proc Natl Acad Sci U S A 109, 13978-13983.
Nauen, DW & Bi, GQ. (2012) Measuring action potential-evoked transmission at individual synaptic contacts. J Neural Eng 9, 036014, doi:10.1088/1741-2560/9/3/036014.
Zhang, JC, Lau, PM & Bi, GQ. (2009) Gain in sensitivity and loss in temporal contrast of STDP by dopaminergic modulation at hippocampal synapses. Proc Natl Acad Sci U S A 106, 13028-13033, doi:10.1073/pnas.0900546106.
Wang, HX, Gerkin, RC, Nauen, DW & Bi, GQ. (2005) Coactivation and timing-dependent integration of synaptic potentiation and depression. Nat Neurosci 8, 187-193.
Lau, PM & Bi, GQ. (2005) Synaptic mechanisms of persistent reverberatory activity in neuronal networks. Proc Natl Acad Sci U S A 102, 10333-10338.
Bi, GQ & Rubin, J. (2005) Timing in synaptic plasticity: from detection to integration. Trends Neurosci 28, 222-228.
Berninger, B & Bi, GQ. (2002) Synaptic modification in neural circuits: a timely action. Bioessays 24, 212-222.
Bi, GQ & Poo, MM. (2001) Synaptic modification by correlated activity: Hebb's postulate revisited. Annu Rev Neurosci 24, 139-166.
Andersen, SS & Bi, GQ. (2000) Axon formation: a molecular model for the generation of neuronal polarity. Bioessays 22, 172-179.
Bi, GQ & Poo, MM. (1999) Distributed synaptic modification in neural networks induced by patterned stimulation. Nature 401, 792-796.
Bi, GQ & Poo, MM. (1998) Synaptic modifications in cultured hippocampal neurons: Dependence on spike timing, synaptic strength, and postsynaptic cell type. J Neurosci 18, 10464-10472.
Bi, GQ, Alderton, JM & Steinhardt, RA. (1995) Calcium-regulated exocytosis is required for cell membrane resealing. J Cell Biol 131, 1747-1758.
Steinhardt, RA, Bi, GQ & Alderton, JM. (1994) Cell membrane resealing by a vesicular mechanism similar to neurotransmitter release. Science 263, 390-393.