大脑皮质抑制性神经环路的发育及其基因调控

项目名称： 大脑皮质抑制性神经环路的发育及其基因调控

项目编号： No.91232723

项目类型： 重大研究计划

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 杨振纲

作者单位： 复旦大学

项目金额： 120万元

中文摘要： 神经系统功能的正常发挥依赖大脑皮质兴奋和抑制的动态平衡。虽然抑制性中间神经元只占皮质神经元总数的20%，但它们与投射神经元所形成的神经环路对维持这一动态平衡起着不可或缺的作用，这也是情感和记忆等高级神经活动的结构基础。近年来发现许多精神神经疾病，如癫痫、自闭症、双向情感障碍及精神分裂症等，与中间神经元发生发育的异常密切相关。脑内中间神经元的起源在啮齿类尚未完全明了，在灵长类则更加知之甚少。本项目拟着重解决以下问题：1. 探讨小鼠大脑皮质中间神经元是否也来自LGE；2. 阐明转录因子Sp8和Coup-TFII对皮质中间神经元发育的调控作用；3. 阐明灵长类皮质中间神经元的起源部位；4. 阐明正常灵长类皮质中间神经元的分类分布规律；5. 观察小儿自闭症脑内中间神经元可能的异常状况。这些问题的解决将有助于阐明相关神经精神疾病的物质基础，也将为发现新的预防、诊断和治疗手段提供科学依据和新的思路。

中文关键词： 大脑皮质；灵长类；中间神经元；转录因子；抑制性神经环路

英文摘要： Cortical inhibitory circuits are comprised of a heterogeneous population of interneurons that release GABA onto pyramidal neurons (the principal cells of the neocortex). It is being recognized that cortical interneurons through their maintenance of the excitatory/inhibitory balance in the cerebrum are central to the normal function of the nervous system. In addition, cortical interneurons have been implicated in psychiatric and neurological disorders including epilepsy, schizophrenia, bipolar disorders and autism. The embryonic basal telencephalon primarily consists of the medial, lateral and caudal ganglionic eminence (MGE, LGE and CGE respectively). Recent studies suggest that the MGE and CGE produce the vast majority of cortical interneurons. However, it remains unknown whether the LGE also generates a subpopulation of interneurons for the cerebral cortex, and whether primate cortical interneurons are mainly derived from the embryonic basal telencephalon. Aim 1 will address these important gaps in our understanding of the development of cortical interneurons in rodents. Our preliminary results suggest that the LGE also generates some Sp8+/Coup-TFII+ cortical interneurons. Aim 2 will explore the function role of Sp8 and Coup-TFII in the development of cortical interneurons using genetic approaches. In addition

英文关键词： cerebral cortex；primates；interneurons；transcription factors；inhibitory circuits