dcf1基因剔除介导焦虑行为机制的研究

项目名称： dcf1基因剔除介导焦虑行为机制的研究

项目编号： No.81471162

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 文铁桥

作者单位： 上海大学

项目金额： 90万元

中文摘要： 精神类疾病与大脑特定神经回路功能密切相关，焦虑症是最为常见精神疾病之一，然而，对此病发生机制的认识尚未清楚。我们的前期研究发现当dcf1基因敲除，小鼠大脑皮层神经细胞迁移障碍，隔膜萎缩，侧脑室显著增大，小鼠伴随焦虑行为，提示神经回路功能异常可能是重要原因。本项目利用dcf1基因剔除小鼠模型，将光遗传技术与神经电生理检测相结合，研究基于dcf1缺失导致的皮层、隔膜、海马发育障碍的神经回路。通过胚胎电转，归属皮层迁移障碍的细胞类型；采用AAV-ChR2载体，研究皮层间以及隔膜、海马萎缩区域的神经元投射；采用AAV-Cre-inducible系统证实神经回路投射与信号改变；通过光遗传特异性激活与抑制特定神经回路，进行高架十字、开场行为测试，判断焦虑行为变化。通过病毒载体送还dcf1基因营救（rescue），实现电生理信号、焦虑行为的恢复，最终阐明Dcf1缺失介导焦虑行为机制。

中文关键词： 神经发育；大脑皮层；神经回路；光遗传；焦虑

英文摘要： Mental illness is closely related to brain specific neural circuit function,while anxiety disorders are one of the most common mental illness. However, understanding the pathogenesis of this disease is not yet clear. Our previous study found that when dcf1 gene knockout, cortical neurons migration in mouse was obstacled, diaphragm shrinking and the lateral ventricles increasing, resulting in an anxiety behavior.It suggests that the neural circuit dysfunction may be an important reason. Using dcf1 knockout mouse model in this project, we will combine the optogenetics and nerve electrophysiological testing to study neural circuits on the cortex , the diaphragm, the hippocampus induced by lack of dcf1. By embryo electroporation, cortical cell types in migrate disorder will be classified. By AAV-ChR2 vector, neurons projecting will be indicated among the cortex, diaphragm, hippocampal atrophy area. AAV-Cre-inducible system is used to demonstrate neural circuits projection and signal changes. Through specific activation and inhibition to specific genetic neural circuits by optogenetics, anxiety behavior will be tested in Elevated Plus to determine anxiety behavior change. Return dcf1 by viral vector gene is used to rescue electrophysiological signals and anxious behavior, and ultimately to clarify anxious behavior mediated mechanism mediated by dcf1 knockout.

英文关键词： Neural development;Cerebral cortex;Circuits;Optogenetics;Anxiety