Laminar and dorsoventral molecular organization of the medial entorhinal cortex revealed by large-scale anatomical analysis of gene expression.
Laminar and dorsoventral molecular organization of the medial entorhinal cortex revealed by large-scale anatomical analysis of gene expression.
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DOI：
10.1371/journal.pcbi.1004032
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发表时间：
2015-01
影响因子：
4.3
通讯作者：
Nolan MF
中科院分区：
文献类型：
--
作者：
Ramsden HL;Sürmeli G;McDonagh SG;Nolan MF
内侧entheral型皮层（MEC）中的神经回路编码动物在空间中的位置和方向。分子成分为了解决这一问题，我们开发了一个新的计算管道，以进行高通量分析，并在层压范围内对原位杂交（ISH）图像进行比较，我们将此管道应用于ISH数据。 and reveals its laminar and dorsoventral organization. We propose a new molecular basis for distinguishing the deep layers of the MEC and show that their similarity to corresponding layers of neocortex is greater than that of superficial layers. Our analysis identifies ion channel-, cell adhesion- and synapse-related genes as candidates for functional differentiation of MEC layers and for encoding of spatial information at different scales along the dorsoventral axis of the MEC。我们还揭示了与疾病病理学相关的基因的层状组织，并在原理上倾向于II层神经退行性病理。空间表示的比例。
在专门的大脑区域内，具有不同功能的大脑认知的功能是在层次和梯度中进行的开发一种解决此问题的新计算管道。阿尔茨海默氏病。我们的计算管道可能对大脑解剖结构进行高通量和高分辨率分析。
Neural circuits in the medial entorhinal cortex (MEC) encode an animal’s position and orientation in space. Within the MEC spatial representations, including grid and directional firing fields, have a laminar and dorsoventral organization that corresponds to a similar topography of neuronal connectivity and cellular properties. Yet, in part due to the challenges of integrating anatomical data at the resolution of cortical layers and borders, we know little about the molecular components underlying this organization. To address this we develop a new computational pipeline for high-throughput analysis and comparison of in situ hybridization (ISH) images at laminar resolution. We apply this pipeline to ISH data for over 16,000 genes in the Allen Brain Atlas and validate our analysis with RNA sequencing of MEC tissue from adult mice. We find that differential gene expression delineates the borders of the MEC with neighboring brain structures and reveals its laminar and dorsoventral organization. We propose a new molecular basis for distinguishing the deep layers of the MEC and show that their similarity to corresponding layers of neocortex is greater than that of superficial layers. Our analysis identifies ion channel-, cell adhesion- and synapse-related genes as candidates for functional differentiation of MEC layers and for encoding of spatial information at different scales along the dorsoventral axis of the MEC. We also reveal laminar organization of genes related to disease pathology and suggest that a high metabolic demand predisposes layer II to neurodegenerative pathology. In principle, our computational pipeline can be applied to high-throughput analysis of many forms of neuroanatomical data. Our results support the hypothesis that differences in gene expression contribute to functional specialization of superficial layers of the MEC and dorsoventral organization of the scale of spatial representations. Higher brain functions such as spatial cognition are carried out in specialized brain areas. Within a specialized brain area nerve cells with different functions are organized in layers and gradients. It is possible that this topographical organization reflects underlying differences in molecular organization of the brain. However, systematic comparison of the expression patterns of tens of thousands of genes at the resolution of layers and borders is challenging. Here we develop a new computational pipeline that addresses this problem. We apply this pipeline to analysis of the medial entorhinal cortex (MEC), a brain structure that is important for spatial cognition. Our analysis shows that the MEC is highly organized at a molecular level, identifies related groups of genes that might underlie functional specialization, and implicates energy-related genes in vulnerability of certain neuronal populations to neurological disorders including Alzheimer’s disease. Our computational pipeline may have general utility for high-throughput and high-resolution analysis of brain anatomy. Our results support the notion that molecular differences contribute to functional specialization of higher cognitive circuits.
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影响因子：
3.1
作者：
Canto CB;Wouterlood FG;Witter MP
通讯作者：
Witter MP
影响因子：
4.2
作者：
Berchtold NC;Sabbagh MN;Beach TG;Kim RC;Cribbs DH;Cotman CW
通讯作者：
Cotman CW
影响因子：
16.2
作者：
Belgard TG;Marques AC;Oliver PL;Abaan HO;Sirey TM;Hoerder-Suabedissen A;García-Moreno F;Molnár Z;Margulies EH;Ponting CP
通讯作者：
Ponting CP
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
14.9
作者：
Basu SN;Kollu R;Banerjee-Basu S
通讯作者：
Banerjee-Basu S