Eph-ephrin受体介导的情感和记忆相关神经环路的发育机制

项目名称： Eph-ephrin受体介导的情感和记忆相关神经环路的发育机制

项目编号： No.91232704

项目类型： 重大研究计划

立项/批准年度： 2013

项目学科： 神经、认识与心理学

项目作者： 徐楠杰

作者单位： 上海交通大学

项目金额： 70万元

中文摘要： 情感和学习记忆功能所依赖的神经环路是经过长期发育而形成的。在这个过程中,分别表达酪氨酸激酶受体家族EphB和其配体ephrin-B的神经元细胞相互接触介导了神经的连接和突触的形成，进而发育成为支持脑功能的神经环路。不仅如此，EphB和ephrin-B还持续大量表达在突触部位，通过与NMDA受体相互作用，直接调节情绪，学习和记忆等神经功能。本项目运用EphB和ephrin-B基因敲除和一系列基因突变敲入小鼠，结合组织形态学，疾病模型和电生理技术等多学科综合手段，围绕环路神经发育和功能这一核心科学问题，深入探讨EphB和ephrin-B在早期神经环路发育，成年突触NMDA受体介导的神经功能调节，阿尔茨海默症脑中的神经环路异常发育等不同方面的重要作用。本研究有助于理解神经环路的发育调节的新机制并且带来对于神经退行性疾病新的治疗靶点。

中文关键词： 杏仁核；ephrin-B3；本能恐惧；树突棘；海马

英文摘要： Emotion, learning and memory dependent neural circuits are formed through long-time developmental peroid. During the progress, EphB tyrosine receptor kinases and their ligand ephrin-Bs mediate neuron-neuron contact, which initiats nerve wiring and synapse formation and allows neural circuit formed to support brain funciton. Moreover, Ephs and ephrin-Bs continue to express highly at synapses and modulate emotion, learning and memory through interacting with NMDA receptor. The proposed studies are mainly focused on development and function of neural circuits by using a series of Eph/ephrin knockout/knockin mice combined with morphology, disease related animal model, electrophysiology and behavioral test to clarify the precise roles of EphB and ephrin in early developmental stage, and adult stage for modulation of neural NMDA receptor modulation at synapses, as well as in Alzheimer''s Disease for abnormal development of neural circuits . The study should lead to an increased understanding of new mechanisms for neural cricuit developmental modulation and noval therapeutic targets for neurodegeneration diseases.

英文关键词： Amygdala；ephrin-B3；innate fear；spine；hippocampus