Effects of neural precursor lineage on pyramidal neuron function and morphology

神经前体谱系对锥体神经元功能和形态的影响

• 批准号: 8837794
• 负责人: Tarik F Haydar
• 金额: $ 24.56万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8837794
• 关键词: Address; Affinity; Autistic Disorder; Axon; Brain; Cell Lineage; Cell division; Cells; Cerebral cortex; Characteristics; Cognitive; Collaborations; Color; Complex; Contralateral; Data; Dendritic Spines; Development; Developmental Disabilities; Diagnosis; Down Syndrome; Electrophysiology (science); Electroporation; Elements; Excitatory Synapse; Exhibits; Fragile X Syndrome; Frequencies; Gene Expression; Genetic; Heterogeneity; Image; Immunofluorescence Immunologic; Immunohistochemistry; Individual; Inhibitory Synapse; Ipsilateral; Kinetics; Label; Laboratories; Lead; Maps; Membrane; Molecular; Morphology; Nature; Neocortex; Neuroglia; Neurons; Parents; Pattern; Play; Population; Population Heterogeneity; Positioning Attribute; Property; Radial; Resolution; Role; Specificity; Stem cells; Stream; Synapses; Techniques; Testing; Three-Dimensional Imaging; Time; Ventricular; Whole-Cell Recordings; Work; base; biocytin; brain malformation; cell type; density; developmental disease; disability; excitatory neuron; hippocampal pyramidal neuron; image reconstruction; in vivo; interdisciplinary approach; lateral ventricle; neocortical; nerve stem cell; nervous system disorder; neural precursor cell; neurogenesis; novel; patch clamp; postsynaptic; precursor cell; presynaptic; programs; public health relevance; tool; transcription factor

DESCRIPTION (provided by applicant): Excitatory neurons of the cerebral cortex are generated prenatally from a diverse group of neural precursors, some of which have only been identified recently. Radial glia stem cells (RGCs) generate neurons directly and at least three separate lineages of Intermediate Neural Precursor Cells (IPCs), which are themselves produced from RGC, also produce neurons. Intriguingly, neurons within each cortical lamina are derived from these different parent cells. The reason why the neocortex requires so many individual precursor cell types, and whether the diverse ancestry of neurons within each layer plays a functional role in neocortical circuitry, has not been established. The numbers of IPCs are thought to be abnormal in several developmental disabilities, including Fragile X and Down's syndromes. In this project, we identify specific lineages of neocortical pyramidal neurons with novel genetic fate mapping tools and determine their structural, functional and connectional characteristics with patch clamp electrophysiology and high resolution 3D imaging. Our preliminary data indicate that neurons from individual precursor lineages, even within the same lamina, are imparted with specific functional properties and that the multiple IPC groups therefore directly underlie neuron and circuit complexity in the neocortex. Morphological and electrophysiological parameters will be quantitatively examined using a multidisciplinary approach and a two-laboratory collaboration.

描述（由申请人提供）：大脑皮质的兴奋性神经元是由一组不同的神经前体在产前产生的，其中一些最近才被发现。放射状神经胶质干细胞（RGC）直接产生神经元，至少有三种独立的中间神经前体细胞（IPC）谱系，它们本身由RGC产生，也产生神经元。有趣的是，每个皮质层内的神经元都来自这些不同的母细胞。为什么新皮层需要如此多的前体细胞类型，以及每层神经元的不同祖先是否在新皮层回路中发挥功能作用，尚未确定。IPC的数量被认为是异常的几个发展障碍，包括脆性X和唐氏综合征。在这个项目中，我们确定新皮层锥体神经元的特定谱系与新的遗传命运映射工具，并确定其结构，功能和连接特性与膜片钳电生理和高分辨率3D成像。我们的初步数据表明，来自单个前体谱系的神经元，即使在同一层内，也被赋予特定的功能特性，因此，多个IPC组直接构成新皮层中神经元和电路复杂性的基础。形态和电生理参数将使用多学科方法和两个实验室的合作进行定量检查。