Project 1: The Origin and Diversity of Human GABAergic Interneurons
项目1:人类GABA能中间神经元的起源和多样性
基本信息
- 批准号:10408733
- 负责人:
- 金额:$ 26.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-07-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAcuteAmygdaloid structureAnatomyArchitectureAreaAutopsyBehaviorBirthBrainCellsChain MigrationsCognitionCollectionDevelopmentDiseaseDorsalEpilepsyEquilibriumEtiologyEvolutionFundingGangliaGene ExpressionGeneticGoalsGrantGrowthHistologicHumanHuman CharacteristicsImageIndividualInfantInfant DevelopmentInterneuronsKnowledgeLeadLifeMedialMolecularMolecular ProfilingNeonatalNeurodevelopmental DisorderNeuronsOutputPathway interactionsPatternPerinatalPopulationPregnancyPropertyProsencephalonRiskRoleRouteSamplingSiteSliceSourceStreamStructureTestingThird Pregnancy TrimesterWorkautism spectrum disordercell growth regulationcingulate gyrusfrontal lobeimprovedinhibitory neuroninterdisciplinary approachmigrationmigratory populationneonatal humannerve stem cellneurogenesisneuron developmentneuropsychiatric disordernovelpostnatalpostnatal humanprogenitorreconstructionsingle-cell RNA sequencingstem cellstime usetranscription factortranscriptomics
项目摘要
PROJECT SUMMARY
Cortical interneurons are a diverse set of local inhibitory cells essential for proper balance of
excitation and inhibition and key to brain function. Abnormal development of interneurons can
lead to severe neuropsychiatric disorders (interneuropathies). Identification of the molecular
pathways and cellular populations implicated in these disorders is necessary to understand their
etiology and to improve our ability to predict which individuals are at risk. Work from our original
grant demonstrated that the infant frontal lobe maintains a large population of migratory
interneurons for several months after birth. This collection of migrating young neurons (Arc)
targets many areas of the infant frontal lobe. These cells contribute importantly to the final
interneuron composition of the human brain (e.g. cingulate gyrus). The human cortex,
therefore, continues to receive interneurons for several months after birth, especially in areas of
higher cognition implicated in neurodevelopmental disorders. Similarly, our recent evidence
shows that the human amygdala continues to receive many young neurons postnatally. These
observations significantly change how we view the development of the infant brain and raise the
need to better understand the origins of human cortical interneurons, including those that
migrate postnatally in the Arc. Young neurons in the human Arc and amygdala are postmitotic
(Ki67-), supporting the hypothesis that they are not generated within these regions. The
expression pattern of regional transcription factors in the Arc, suggests that they come from the
developing human ventral forebrain; the Medial and Caudal Ganglionic Eminences (hMGE and
hCGE). The project's overall goal is to understand how the human GE generates large
numbers and diverse types of cortical interneurons by studying its development during the mid-
late gestation and early postnatal life. We will determine the genetic and molecular properties of
proliferative populations in the hMGE, hLGE, and hCGE using human postmortem brain
samples from neonatal and infant cases (up to 6 months after birth), define how interneuron
subtypes arise in the perinatal human brain. The proposed studies will identify the unique and
sustained properties of human inhibitory neuron development. By using a multi-disciplinary
approach (including transcriptomic, histological, and acute slice cultures), we aim to establish
how interneurons are made in the human brain and provide the fundamental knowledge needed
to understand their role in disease.
项目概要
皮质中间神经元是一组不同的局部抑制细胞,对于适当的平衡至关重要
兴奋和抑制是大脑功能的关键。中间神经元的异常发育可以
导致严重的神经精神疾病(中间神经病)。分子鉴定
与这些疾病有关的途径和细胞群对于了解它们的
病因学并提高我们预测哪些人处于危险之中的能力。源自我们原创的作品
格兰特证明婴儿额叶维持着大量的迁徙
出生后几个月的中间神经元。这个迁移的年轻神经元的集合(Arc)
针对婴儿额叶的许多区域。这些细胞对最终的结果有重要贡献
人脑的中间神经元组成(例如扣带回)。人类的皮质,
因此,出生后几个月继续接受中间神经元,特别是在以下区域
较高的认知能力与神经发育障碍有关。同样,我们最近的证据
研究表明,人类杏仁核在出生后继续接收许多年轻的神经元。这些
观察结果显着改变了我们对婴儿大脑发育的看法,并提高了
需要更好地了解人类皮质中间神经元的起源,包括那些
出生后在弧区迁移。人类弧形和杏仁核中的年轻神经元是有丝分裂后的
(Ki67-),支持了它们不是在这些区域内产生的假设。这
弧区区域转录因子的表达模式表明它们来自
发育人类腹侧前脑;内侧和尾部神经节隆起(hMGE 和
hCGE)。该项目的总体目标是了解人类基因工程如何产生大量的
通过研究皮质中间神经元在中期的发育,了解其数量和不同类型
妊娠晚期和产后早期生活。我们将确定其遗传和分子特性
使用人类死后大脑进行 hMGE、hLGE 和 hCGE 中的增殖群体
新生儿和婴儿病例(出生后 6 个月内)的样本,定义了中间神经元如何
亚型出现在围产期人类大脑中。拟议的研究将确定独特且
人类抑制神经元发育的持续特性。通过使用多学科
方法(包括转录组学、组织学和急性切片培养),我们的目标是建立
中间神经元如何在人脑中产生并提供所需的基础知识
了解它们在疾病中的作用。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Arturo Alvarez-Buylla其他文献
Arturo Alvarez-Buylla的其他文献
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{{ truncateString('Arturo Alvarez-Buylla', 18)}}的其他基金
Clustered protocadherin regulation of cortical interneuron survival circuit assembly and plasticity
簇状原钙粘蛋白对皮质中间神经元生存回路组装和可塑性的调节
- 批准号:
10121089 - 财政年份:2020
- 资助金额:
$ 26.65万 - 项目类别:
Clustered protocadherin regulation of cortical interneuron survival circuit assembly and plasticity
簇状原钙粘蛋白对皮质中间神经元生存回路组装和可塑性的调节
- 批准号:
10472616 - 财政年份:2020
- 资助金额:
$ 26.65万 - 项目类别:
Structure and function of a novel population of regenerating ependymal cells
新型再生室管膜细胞群的结构和功能
- 批准号:
10618162 - 财政年份:2020
- 资助金额:
$ 26.65万 - 项目类别:
Structure and function of a novel population of regenerating ependymal cells
新型再生室管膜细胞群的结构和功能
- 批准号:
10400197 - 财政年份:2020
- 资助金额:
$ 26.65万 - 项目类别:
Clustered protocadherin regulation of cortical interneuron survival circuit assembly and plasticity
簇状原钙粘蛋白对皮质中间神经元生存回路组装和可塑性的调节
- 批准号:
10689086 - 财政年份:2020
- 资助金额:
$ 26.65万 - 项目类别:
Clustered protocadherin regulation of cortical interneuron survival circuit assembly and plasticity
簇状原钙粘蛋白对皮质中间神经元生存回路组装和可塑性的调节
- 批准号:
10264172 - 财政年份:2020
- 资助金额:
$ 26.65万 - 项目类别:
Project 1: The Origin and Diversity of Human GABAergic Interneurons
项目1:人类GABA能中间神经元的起源和多样性
- 批准号:
10221061 - 财政年份:2014
- 资助金额:
$ 26.65万 - 项目类别:
Microglial mechanism of dopaminergic axonal growth - Project 3
多巴胺能轴突生长的小胶质细胞机制 - 项目 3
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10841254 - 财政年份:2014
- 资助金额:
$ 26.65万 - 项目类别:
Interneuron Precursors and the induction of cortical plasticity
中间神经元前体和皮质可塑性的诱导
- 批准号:
9179634 - 财政年份:2014
- 资助金额:
$ 26.65万 - 项目类别:
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