A transcriptional signature of hub connectivity in the mouse connectome
A transcriptional signature of hub connectivity in the mouse connectome
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DOI：
10.1073/pnas.1513302113
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发表时间：
2016-02-02
影响因子：
11.1
通讯作者：
Fornito, Alex
中科院分区：
文献类型：
--
作者：
Fulcher, Ben D.;Fornito, Alex
连通性在整个大脑中分布不均匀。相反，它集中在少数高度连接的神经元上，这些神经元充当网络枢纽。在不同的物种和测量尺度上，这些枢纽显示出密集的互连性，形成了一个核心或“丰富的俱乐部”，整合了解剖学分布的神经系统的信息。在这里，我们表明，小鼠大脑的连接枢纽之间的投射都是中心的（即，它们在神经通信中起重要作用）和昂贵（即，它们在很长的解剖学距离上延伸）网络组织的各个方面，这些方面携带着独特的基因签名。通过分析213个大脑区域的神经元连接以及每对区域之间17,642个基因的转录耦合，我们发现，连接的枢纽对的耦合最高，枢纽和非枢纽之间的连接居中，而连接的非枢纽对的耦合最低。与枢纽连接相关的高转录偶联是由调节ATP的氧化合成和代谢的基因驱动的，ATP是神经元通信的主要能量货币。这种遗传特征与一般神经元连接性的识别形成对比，神经元连接性由调节神经元、突触和轴突结构和功能的基因驱动。我们的研究结果建立了分子功能和神经元连接的大规模拓扑结构之间的直接联系，表明大脑枢纽显示出基因表达的紧密协调，通常在很长的解剖距离上，这与这些高度活跃的网络元素的代谢要求密切相关。
Connectivity is not distributed evenly throughout the brain. Instead, it is concentrated on a small number of highly connected neural elements that act as network hubs. Across different species and measurement scales, these hubs show dense interconnectivity, forming a core or "rich club" that integrates information across anatomically distributed neural systems. Here, we show that projections between connectivity hubs of the mouse brain are both central (i.e., they play an important role in neural communication) and costly (i.e., they extend over long anatomical distances) aspects of network organization that carry a distinctive genetic signature. Analyzing the neuronal connectivity of 213 brain regions and the transcriptional coupling, across 17,642 genes, between each pair of regions, we find that coupling is highest for pairs of connected hubs, intermediate for links between hubs and nonhubs, and lowest for connected pairs of nonhubs. The high transcriptional coupling associated with hub connectivity is driven by genes regulating the oxidative synthesis and metabolism of ATP-the primary energetic currency of neuronal communication. This genetic signature contrasts that identified for neuronal connectivity in general, which is driven by genes regulating neuronal, synaptic, and axonal structure and function. Our findings establish a direct link between molecular function and the large-scale topology of neuronal connectivity, showing that brain hubs display a tight coordination of gene expression, often over long anatomical distances, that is intimately related to the metabolic requirements of these highly active network elements.