抑郁症模型及大脑深处刺激在前额叶皮质的突触传递及可能的分子机制

项目名称： 抑郁症模型及大脑深处刺激在前额叶皮质的突触传递及可能的分子机制

项目编号： No.31200771

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学心理学

项目作者： 郭飞

作者单位： 中国科学院上海药物研究所

项目金额： 21万元

中文摘要： 目前对于抑郁症的治疗和患病机制的研究倍受关注，但是对其相关通路和调控机制的研究还有待深入。本项目拟通过电生理的方法，探讨抑郁症模型动物及DBS调控抑郁症突触环路的细胞机制。主要通过三个方面展开研究：（1）通过全细胞膜片钳的方法，分别研究D1和D2受体激活后对KCNQ和Trek钾离子通道的影响。（2）考察抑郁症模型动物PFC内突触环路的生理特征：采用CSD技术，电刺激VTA，考察抑郁症模型动物中脑皮层通路在PFC各层的诱发电位；在体标记VTA投射到PFC的细胞，考察标记细胞的EPSCs；并电刺激PFC的表层，记录第Ⅴ锥体细胞的EPSCs,了解皮层内突触连接的变化；最后考察不同多巴胺受体亚型对EPSCs的影响及可能的分子机制。（3）脑深处刺激SCC，通过行为测试观察该刺激是否可以使抑郁动物得到恢复，并考察VTA投射到PFC标记细胞的EPSCs和皮层表层投射到第Ⅴ层锥体细胞的EPSCs。

中文关键词： 抑郁症；前额叶；深部脑刺激；突触可塑性；

英文摘要： Recently , the treatment for depression and it's causes have been widely focusing on, however, what is the related pathway and mechanism is needed to go deep. In this project, we want to examine synaptic circuitry underlie the model of depression and DBS-treated depression using the method of electrophysiology. Three major points would be investigated in this study. 1) The effect of agonist of D1 and D2 receptors on classic K+ channel (KCNQ and Trek) using the method of whole cell clam patch. 2) Examine the property of synaptic circuitry in PFC in the depressive animals. First, the evoked potentials in PFC are induced by the stimulation of VTA. The technique of CSD allows us to know the laminar profile and figure out which layer is the VTA-input layer. Second, the EPSCs of VTA-projecting neurons in PFC are recorded. And the EPSCs of layer Ⅴ pyramidal neurons are recorded induced by the stimulation of surface layer to examine the changes of the introcortical synaptic circuitry. Finally, the effect of two opamine receptor subunits on EPSCs are examined to know it's potential mechanism. 3) examine whether the behavioral performances could be recovered in depressive animals induced by deep brain stimulation in SCC. Also, the EPSCs of VTA-projecting neurons and layer Ⅴ neurons evoked by the stimulation of VTA and sur

英文关键词： Depression；Prefrontal cortex；Deep brain stimulation；Synaptic plasticity；