MICROGLIA-SYNAPSE INTERACTIONS: THEIR ROLES IN THE BRAIN'S ADAPTATION TO ENVIRONMENTAL CHALLENGES

小胶质细胞-突触相互作用：它们在大脑适应环境挑战中的作用

• 批准号: RGPIN-2014-05308
• 负责人: Tremblay, MarieEve
• 金额: $ 2.46万
• 依托单位: University of Victoria
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=708149
• 关键词: MICROGLIA; SYNAPSE; INTERACTIONS; THEIR; ROLES

A series of discoveries spanning the last few years have challenged our view of microglia, the brain immune cells, showing their active and positive contribution to normal brain functioning. In particular, my work revealed that microglia continuously interact with synaptic elements in an experience-dependent manner, and eliminate by phagocytosis a subset of axon terminals and dendritic spines, thus suggesting an unexpected role for these cells in the neuronal circuit remodelling that is required for learning and memory. Nevertheless, the molecular signals regulating their interactions with synapses, much as their functional relevance, still remain undetermined at this early stage of investigation in the field. In this context, the long term objective of my research program is to elucidate microglial contribution -in cooperation with the various cell types making up the brain- to normal brain functions including learning and memory. As a new investigator, my first NSERC grant will test the hypothesis that release of corticosterone (the main glucocorticoid hormone in rodents) induced by behavioural stress interferes with memory formation and learning by acting on microglial remodelling of synaptic structures.

过去几年跨越的一系列发现挑战了我们对小胶质细胞，脑免疫细胞的看法，显示出它们对正常脑功能的积极和积极的贡献。特别是，我的工作表明，小胶质细胞以经验依赖性的方式与突触元素连续相互作用，并通过吞噬作用消除了轴突末端和树突状棘的子集，因此表明这些细胞在神经元电路中的意外作用是学习和记忆所必需的。然而，在该领域的研究早期阶段，与其功能相关性一样，调节其与突触的相互作用的分子信号仍然不确定。在这种情况下，我的研究计划的长期目标是阐明小胶质贡献 - 与构成大脑到正常脑功能的各种细胞类型的合作，包括学习和记忆。作为一名新研究者，我的第一个NSERC赠款将检验以下假设：行为应力干扰记忆形成和学习通过对突触结构的小胶质重塑作用，释放了释放的皮质酮（啮齿动物中的主要糖皮质激素激素）。