Genetic Determinants of Local Circuit Organization

摘要/摘要 在整个中枢神经系统中，亚群的位置和层状组织的多样性 神经元及其突触回路是功能特异性的基础，这在视觉上是显而易见的。 调节低分辨率图像与高分辨率图像的路径。电路的规格化程度 嗅球仍然存在争议。功能分析表明气味诱导的地形 活动，但这集中在肾小球，在那里感觉神经元轴突表达相同 气味感受器汇聚和终止；关于气味特异性的报道有相互矛盾的数据 二尖瓣细胞和球内更深的放射状和水平环状结构。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，但考虑到单个肾小球体积的异质性，这可能是一种 误导性的概括。支配单个肾小球的二尖瓣细胞是否有共同的 出生日期、迁徙时间或分子表型也不清楚。第二，虽然 有几项研究检查了球的去传入，但我们对此知之甚少 影响树突及其突触精细结构组织的营养机制 组织。简而言之，我们的首要目标是更好地了解胚胎和 嗅球初级细胞组织潜在的围产期事件。要实现 这一目标我们的具体目标概括为：1)确定目标的基本原则 二尖瓣细胞亚群对肾小球的影响；2)建立出生日期、细胞凋亡之间的关系 细胞死亡，以及嗅球二尖瓣细胞的地形图；以及3)检验营养 促进二尖瓣细胞分化和成熟的机制，尤其是脑源性神经营养因子。 这项工作提供了对与疾病相关的早期发育决定因素的洞察，例如 卡尔曼综合症和自闭症；得出的原则也可能与广泛的 皮质发育异常的类别和综合征，如脆性X。

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.