Sorensen Staci A, Bernard Amy, Menon Vilas, Royall Joshua J, Glattfelder Katie J, Desta Tsega, Hirokawa Karla, Mortrud Marty, Miller Jeremy A, Zeng Hongkui, Hohmann John G, Jones Allan R, Lein Ed S
Allen Institute for Brain Science, Seattle, WA 98040, USA.
Cereb Cortex. 2015 Feb;25(2):433-49. doi: 10.1093/cercor/bht243. Epub 2013 Sep 7.
The neocortex contains diverse populations of excitatory neurons segregated by layer and further definable by their specific cortical and subcortical projection targets. The current study describes a systematic approach to identify molecular correlates of specific projection neuron classes in mouse primary somatosensory cortex (S1), using a combination of in situ hybridization (ISH) data mining, marker gene colocalization, and combined retrograde labeling with ISH for layer-specific marker genes. First, we identified a large set of genes with specificity for each cortical layer, and that display heterogeneous patterns within those layers. Using these genes as markers, we find extensive evidence for the covariation of gene expression and projection target specificity in layer 2/3, 5, and 6, with individual genes labeling neurons projecting to specific subsets of target structures. The combination of gene expression and target specificity imply a great diversity of projection neuron classes that is similar to or greater than that of GABAergic interneurons. The covariance of these 2 phenotypic modalities suggests that these classes are both discrete and genetically specified.
新皮质包含多种兴奋性神经元群体，这些群体按层分隔，并且可根据其特定的皮质和皮质下投射靶点进一步定义。本研究描述了一种系统方法，通过结合原位杂交（ISH）数据挖掘、标记基因共定位以及将逆行标记与ISH相结合以检测层特异性标记基因，来鉴定小鼠初级体感皮层（S1）中特定投射神经元类别的分子关联。首先，我们鉴定出了一大组对每个皮质层具有特异性且在这些层内呈现异质性模式的基因。以这些基因为标记，我们发现了大量证据，表明基因表达与第2/3层、第5层和第6层中的投射靶点特异性存在共变关系，单个基因标记着投射到特定靶点结构子集的神经元。基因表达与靶点特异性的结合意味着投射神经元类别的巨大多样性，这与GABA能中间神经元的多样性相似或更大。这两种表型模式的共变表明这些类别既是离散的又是由基因指定的。
