Formation of the earliest circuits in the cerebral cortex

大脑皮层最早回路的形成

• 批准号: G0900901/1
• 负责人: Zoltan Molnar
• 金额: $ 191.12万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0900901%2F1
• 关键词: Formation; earliest; circuits; cerebral; cortex

Building the brain is like erecting a huge building. The construction requires a dynamic scaffold which is built and modified along with the final permanent structure. During and after the completion of the building, the scaffold has to be dismantled at the right places and at the right time. The subplate, formed by the earliest generated and largely transient cortical neurons, is the developmental scaffold of the cortex of the brain, and disruption of these cells may be the source of many developmental disorders and therefore a fundamental topic to study. Developmental disorders of the cerebral cortical (schizophrenia, autism, attention deficit/hyperactivity disorder, ADHD) and hypoxic injuries around the time of birth (periventricular leucomalacia, PVL) involve cells of the subplate. The Molnar group has been investigating the integration of subplate cells into the intracortical and extracortical circuitry, their neurochemical properties and physiological characteristics over the last 16 years. Just like the building scaffold has to change dynamically during the course of the construction, so does the structure and circuitry formed by subplate cells during development. We aim to characterize gene expression patterns in the subplate throughout the life of a mouse and optimize some of these markers for use on human tissue. For subgroups of subplate cells identified by these markers, we aim to characterize their structure and projection pattern and how they function as part of the complex circuitry that is the mouse brain. These approaches require much specialised skills, which are beyond the scope of a single research group. The proposed collaboration will foster the interactions between a physiology laboratory (Dr Ole Paulsen) and a cellular/molecular and anatomical group and will open opportunities for the initiation of clinical applications in neuro-imaging, psychiatry, and neuropathology.

建造大脑就像建造一座巨大的建筑。施工需要动态脚手架，动态脚手架与最终的永久结构一起沿着建造和修改。在建筑物完工期间和之后，脚手架必须在正确的地点和正确的时间拆除。由最早产生的且主要是短暂的皮质神经元形成的亚板是大脑皮质的发育支架，并且这些细胞的破坏可能是许多发育障碍的来源，因此是研究的基本课题。大脑皮质发育障碍（精神分裂症、自闭症、注意力缺陷/多动障碍、ADHD）和出生前后的缺氧性损伤（脑室周围白质软化症、PVL）涉及基板细胞。在过去的16年里，Molnar小组一直在研究亚板细胞整合到皮质内和皮质外回路中，它们的神经化学性质和生理特征。就像建筑脚手架在建造过程中必须动态变化一样，亚板细胞在发育过程中形成的结构和电路也是如此。我们的目标是在小鼠的整个生命过程中表征亚板中的基因表达模式，并优化其中一些标记物用于人体组织。对于由这些标记物鉴定的亚板细胞亚群，我们的目标是表征它们的结构和投射模式，以及它们如何作为小鼠大脑复杂电路的一部分发挥作用。这些方法需要许多专业技能，这超出了一个单一研究小组的范围。拟议的合作将促进生理学实验室（Ole Paulsen博士）与细胞/分子和解剖学小组之间的互动，并将为神经成像，精神病学和神经病理学的临床应用提供机会。