视皮层发育突触稳态机制的研究

项目名称： 视皮层发育突触稳态机制的研究

项目编号： No.31271174

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 赵从健

作者单位： 中国人民解放军第三军医大学

项目金额： 75万元

中文摘要： 突触稳态可塑性（HSP）作为视皮层发育突触可塑性主要调控机制，通过调节神经环路整体兴奋性，从而保持神经网络适度兴奋，防止长时间处于过度兴奋或抑制的状态。由于研究手段的匮乏，在活体水平研究HSP中突触前膜的调控，及兴奋性和抑制性神经元二者之间相互作用的研究仍为空白。借助我们对研究技术瓶颈的突破,使用SypGCaMP2（突触前钙离子）和SypHy（递质释放）我们在体外模型中首次证实突触前参与了HSP，并揭示突触前钙离子为HSP突触前调节机制的关键。该课题将使用更灵敏、新一代SypGCaMP5/PSD-85-GCaMP5和SypHy结合在体转基因、双光子图像技术，以视皮层发育关键期谷氨酸能和GABA能突触及神经元为研究对象，研究突触前、后钙离子在视皮层发育HSP调节机理。并在离体和活体模型系统地研究突触稳态可塑性，尤其兴奋性或抑制性突触前、后膜及胞体的功能变化及二者之间相互作用的时空关系。

中文关键词： 视皮层；突触；稳态平衡；钙离子；异质性

英文摘要： Visual experience plays a pivotal role in refining the connectivity of primary visual cortex, but the synaptic plasticity mechanisms that contribute to this refinement are still under debate. Turrigino has recently demonstrated that homeostatic synaptic plasticity scales excitatory and inhibitory synaptic strengths up and down in the cortical networks in vitro. A similar phenomenon has also found in vivo. Furthermore, homeostatic synaptic scaling in experience-dependent plasticity has been demonstrated in vivo using a classic sensory deprivation paradigm, monocular deprivation (MD) and binocular deprivation (BD) using lid suture. However those studies were not able to dissect presynaptic mechanism due to lack of proper tools. Using cultured hippocampal networks we demonstrated that the presynaptic mechanism is involved in homeostatic synaptic plasticity, that is presynaptic calcium signal is a key control point for regulating synaptic strength in response to chronic changes in network activity. Therefore we will approach this question by manipulating activity in rodent visual cortex through MD, then using our presynaptic and postsynaptic calcium（SypGCaMPs,PSD-95-GCaMPs） and synaptic vesicle fusion reports（SypHy） to measure paired synaptic transmission in vitro and in vivo， which were measured in zebrafish retina

英文关键词： visual cortex；synapse；homeostatic plasticity；calcium；heterogeneity