Glia-mediated control of extracellular GABA/glutamate balance in the developing cortex

神经胶质细胞介导的对发育中皮层细胞外 GABA/谷氨酸平衡的控制

• 批准号: 28299927
• 负责人: Privatdozent Dr. Sergei Kirischuk
• 金额: --
• 依托单位: Institut für Physiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/28299927?language=en
• 关键词: Glia; mediated; control; extracellular; GABA

The principal inhibitory neurotransmitters of the brain, GABA and glycine, operate before synapses are formed. Extracellular GABA concentration ([GABA]e) is regulated via GABA transporters (GATs). Different GAT isoforms show a cell typespecific distribution: GAT-1 was mainly found in neurons, whereas GAT-3 was mainly observed in glia. Our preliminary data shows that the strength and development of GABAergic synaptic transmission (GST) in the immature visual cortex is regulated by the level of extracellular inhibitory amino acids:i) GST at Cajal-Retzius cells, a class of pioneer neurons, was weakened by pharmacological GAT-1 block, whereas GAT-3 inhibition enhanced GABA release,ii) Cortical neurons overexpressing a high-affinity form of the glycine receptor demonstrated reduced GABAergic synaptogenesis.We intend to address the following questions:a) How are the main sources of GABA (vesicular and GATs) spatially arranged in the marginal zone of the developing visual cortex?b) How does GABAergic synaptic activity affect the signaling of nearby astrocytes?c) How do astrocytes modulate GST in the immature cortex?d) What is the role of glial GAT-3 in synapse development?

大脑中主要的抑制性神经递质GABA和甘氨酸在突触形成之前起作用。细胞外GABA浓度（[GABA]e）通过GABA转运蛋白（GATs）调节。不同的GAT亚型显示出细胞类型特异性分布：GAT-1主要见于神经元，而GAT-3主要见于胶质细胞。我们的初步数据表明，未成熟视皮层中GABA能突触传递（GST）的强度和发展受细胞外抑制性氨基酸水平的调节：i）Cajal-Retzius细胞（一类先驱神经元）的GST被药物GAT-1阻断所削弱，而GAT-3抑制增强GABA释放，ii）过度表达高亲和力形式的甘氨酸受体的皮质神经元表现出减少的GABA能突触发生。a）GABA的主要来源（囊泡和GATs）在发育中的视皮层边缘区的空间分布如何？B）GABA能突触活动如何影响附近星形胶质细胞的信号传导？c）星形胶质细胞如何调节未成熟皮质中的GST？d）胶质细胞GAT-3在突触发育中的作用是什么？