Genetic Determinants of Local Circuit Organization

局部电路组织的遗传决定因素

• 批准号: 8277998
• 负责人: Charles A Greer
• 金额: $ 42.97万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-12-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8277998
• 关键词: Address; Afferent Neurons; Apical; Apoptosis; Apoptotic; Autistic Disorder; Axon; Brain; Brain-Derived Neurotrophic Factor; Categories; Cell Death; Cells; Code; Conflict (Psychology); Cortical Dysplasia; Data; Date of birth; Deafferentation procedure; Dendrites; Dendritic Cells; Dendrodendritic Synapse; Development; Disease; Drosophila genus; Embryo; Employee Strikes; Event; Foundations; Fragile X Syndrome; Genetic Determinism; Goals; Heterogeneity; Image; Individual; Interneurons; Intervention; Lobe; Location; Mediating; Modeling; Nervous system structure; Neuraxis; Neurons; Odors; Olfactory Pathways; Perinatal; Positioning Attribute; Process; Property; Radial; Reporting; Resolution; Role; Seminal; Sensory; Series; Specificity; Synapses; Syndrome; System; Testing; Visual Pathways; Work; developmental disease; granule cell; insight; migration; molecular marker; molecular phenotype; nerve supply; neural circuit; neurogenesis; olfactory bulb; receptive field; receptor; synaptogenesis

ABSTRACT/SUMMARY Throughout the CNS diversity in the location and laminar organization of subpopulations of neurons and their synaptic circuits underlies functional specificity, as is evident in the visual pathways mediating low versus high resolution images. The degree of circuit specification in the olfactory bulb remains controversial. Functional analyses suggest a topography of odor-induced activity, but this has focused on the glomeruli where sensory neuron axons expressing the same odor receptor converge and terminate; conflicting data has been reported on the odor-specificity of mitral cells and the deeper radial and horizontal circuits in the bulb. Our proposal has two primary goals. First, there is little information on the innervation of individual glomeruli by subsets of mitral cells. Estimates suggest that each glomerulus is innervated by a subset of 25 mitral cells, but given the heterogeneity in the volume of individual glomeruli, this is likely a misleading generalization. Whether the mitral cells innervating single glomeruli share a common birth date, migratory timeframe or molecular phenotype are also not known. Second, while several studies have examined deafferentation in the bulb, we know comparatively little about trophic mechanisms influencing the fine structural organization of dendrites and their synaptic organization. In brief, our overarching goal is a better understanding of the embryonic and perinatal events underlying the primary cellular organization in the olfactory bulb. To achieve this goal our specific aims are summarized as: 1) Determine the principles underlying targeting of glomeruli by subsets of mitral cells; 2) Establish the relationship between birth date, apoptotic cell death, and topography of olfactory bulb mitral cells; and 3) Test the hypothesis that trophic mechanisms, in particular BDNF, contribute to the differentiation and maturation of mitral cells. This work provides insight into determinants of early development relevant to diseases such as Kallman's syndrome and autism; the principles derived are also likely relevant to broad categories of anomalous cortical development and syndromes such as Fragile-X.

摘要/总结 在中枢神经系统中， 神经元及其突触回路是功能特异性的基础，这在视觉神经元中是显而易见的。 介导低分辨率图像与高分辨率图像的通路。电路规格的程度， 嗅球仍然存在争议。功能分析表明，气味诱导的拓扑结构 活动，但这集中在肾小球，感觉神经元轴突表达相同的 气味受体收敛和终止;关于气味特异性的报道存在矛盾的数据 僧帽细胞以及球状物中较深的径向和水平回路。我们的建议有两个 主要目标。首先，关于单个肾小球的神经支配的信息很少， 二尖瓣细胞的亚群。据估计，每个肾小球由25个亚群支配。 二尖瓣细胞，但考虑到个体肾小球体积的异质性，这可能是一个 误导性的概括支配单个肾小球的二尖瓣细胞是否具有共同的 出生日期、迁徙时间表或分子表型也不清楚。第二，虽然 几项研究已经检查了球的传入神经阻滞，我们对球的传入神经阻滞知之甚少。 影响树突及其突触精细结构组织的营养机制 organization.简而言之，我们的首要目标是更好地了解胚胎和 围产期事件潜在的初级细胞组织在嗅球。实现 这一目标我们的具体目标概括为：1）确定目标制定的原则 2）建立出生日期、细胞凋亡与肾小球的关系 细胞死亡和嗅球僧帽细胞的拓扑结构;和3）测试营养性的假设， BDNF的作用机制，特别是BDNF，有助于二尖瓣细胞的分化和成熟。 这项工作提供了对与疾病相关的早期发育决定因素的深入了解， 卡尔曼综合征和自闭症;所得出的原则也可能与广泛的 异常皮质发育和综合征的类别，如脆性X。