The Developmental Origins of Cerebral Cortical Expansion in Evolution & Disorder

进化中大脑皮层扩张的发育起源

• 批准号: 8125459
• 负责人: Christine J Charvet
• 金额: $ 4.63万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-07 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8125459
• 关键词: Accounting; Address; Adult; Amygdaloid structure; Autistic Disorder; Back; Brain; Brain region; Cell Cycle; Cell Cycle Kinetics; Cerebral cortex; Cerebrum; Databases; Defect; Development; Embryo; Event; Evolution; Exhibits; Gene Expression; Histones; Human; Individual; Label; Limbic System; Magnetic Resonance Imaging; Mammals; Maps; Mus; Neurologic; Papio; Patients; Pattern; Population; Primates; Principal Component Analysis; Proliferating Cell Nuclear Antigen; Proliferation Marker; Relative (related person); Rest; Rodent; Structure; Telencephalon; Testing; Time; Tissues; Variant; Work; cost; frontal lobe; insight; neurogenesis; olfactory bulb; species difference

DESCRIPTION (provided by applicant): One aim of the present proposal is to determine how evolution altered development to endow primates with an expanded cerebral cortex and a reduced limbic system (e.g., the olfactory bulb, septum, amygdala) compared with other mammals (e.g. rodents). Previous work has shown that cortical neurogenesis is protracted whereas neurogenesis in the limbic system is advanced in primates compared with rodents. However, these findings do not preclude the possibility that events prior to neurogenesis onset account for adult variations in the size of the cortex and limbic system across species. The expanded cerebral cortex and reduced limbic system of primates might emerge before neurogenesis begins. Specifically, I will test whether the expansion of the cerebral cortex in primates is due to changes in brain patterning and/or cell cycle kinetics. Another major aim of the present proposal is to use structural magnetic resonance imaging to examine the variation in brain region size of humans in adulthood. Compared with evolutionarily stable structures, structures with increased variability between species may also be more variable within a species. Individual variation likely comes with benefits (e.g., adaptive changes) as well as costs. For example, the abnormally large frontal cortex found in patients with autism may be indicative of an extreme end of a natural range. Understanding the developmental mechanisms that underlie the expansion of the brain in primates and its natural variation will enhance our understanding of the basic principles underlying adaptive and mal-adaptive changes in development. PUBLIC HEALTH RELEVANCE: Autism is associated with an enlargement of the cerebral cortex and reduction of some limbic structures. These developmental alterations might arise because of alterations in brain patterning or developmental timing but we currently understand very little about these neurological defects. Understanding how brains change in evolution will help elucidate how brains change mal-adaptively.

描述（由申请人提供）：本提案的目的之一是确定演变如何改变发育剂，以赋予具有扩展的大脑皮层和降低的边缘系统（例如，嗅球，隔膜，杏仁核）与其他哺乳动物（例如其他哺乳动物）（例如，Rodents）相比。先前的工作表明，与啮齿动物相比，在灵长类动物中，皮层神经发生是长时间的，而在边缘系统中的神经发生是先进的。但是，这些发现并不排除神经发生之前事件的可能性，即在物种跨物种的皮质和边缘系统大小的成年变化中。在神经发生开始之前，可能会出现膨胀的大脑皮层和降低的灵长类动物的边缘系统。具体而言，我将测试灵长类动物中大脑皮层的膨胀是否是由于脑模式和/或细胞周期动力学的变化。 本提案的另一个主要目的是使用结构磁共振成像来检查成年后人类大脑区域大小的变化。与进化稳定的结构相比，物种之间具有变化差异的结构在一个物种内也可能更具变化。个体差异可能带来好处（例如自适应变化）和成本。例如，在自闭症患者中发现的异常大额叶皮质可能表明自然范围的极端端。了解灵长类动物中大脑及其自然变化的发展的发展机制将增强我们对发展中适应性和马力自适应变化的基本原理的理解。 公共卫生相关性：自闭症与大脑皮层的扩大和一些边缘结构的减少有关。这些发展变化可能是由于脑模式或发育时机的改变而发生的，但目前我们对这些神经系统缺陷的了解很少。了解大脑在进化中的变化将有助于阐明大脑如何改变恶性变化。