A novel approach to the functional classification of retinal ganglion cells.
A novel approach to the functional classification of retinal ganglion cells.
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DOI：
10.1098/rsob.210367
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发表时间：
2022-03
期刊：
影响因子：
5.8
通讯作者：
Sernagor E
中科院分区：
文献类型：
--
作者：
Hilgen G;Kartsaki E;Kartysh V;Cessac B;Sernagor E
视网膜神经元在结构、功能和遗传特性上具有显著的多样性。对这些细胞进行分类是一项具有挑战性的任务，需要多模式方法。在这里，我们介绍了一种新的方法，视网膜神经节细胞（RGC）的分类，结合免疫组织化学和大规模的视网膜电生理学的基础上药物遗传学。我们的新策略允许对共享基因表达的细胞进行分组，并了解这些细胞类别如何对基本和复杂的视觉场景做出反应。我们的方法包括几个连续的步骤。首先，使用兴奋性DREADD（设计药物专门激活的设计受体），在共表达某种基因（Scnn1a或Grik 4）的RGCs中增加尖峰放电频率，以挑选出特异性源自这些细胞的活性。然后将其尖峰位置与事后免疫染色相结合，以明确表征其解剖学和功能特征。我们将这些孤立的RGC分组为多个集群的基础上尖峰列车的相似性。使用这种新方法，我们能够将先前存在的表达Grik 4的RGC类型列表扩展到总共8种，并且我们首次提供了13种表达Scnn1a的RGC的表型描述。这里获得的见解和方法不仅可以指导RGC分类，还可以指导其他大脑区域的神经元分类挑战。
Retinal neurons are remarkedly diverse based on structure, function and genetic identity. Classifying these cells is a challenging task, requiring multimodal methodology. Here, we introduce a novel approach for retinal ganglion cell (RGC) classification, based on pharmacogenetics combined with immunohistochemistry and large-scale retinal electrophysiology. Our novel strategy allows grouping of cells sharing gene expression and understanding how these cell classes respond to basic and complex visual scenes. Our approach consists of several consecutive steps. First, the spike firing frequency is increased in RGCs co-expressing a certain gene (Scnn1a or Grik4) using excitatory DREADDs (designer receptors exclusively activated by designer drugs) in order to single out activity originating specifically from these cells. Their spike location is then combined with post hoc immunostaining, to unequivocally characterize their anatomical and functional features. We grouped these isolated RGCs into multiple clusters based on spike train similarities. Using this novel approach, we were able to extend the pre-existing list of Grik4-expressing RGC types to a total of eight and, for the first time, we provide a phenotypical description of 13 Scnn1a-expressing RGCs. The insights and methods gained here can guide not only RGC classification but neuronal classification challenges in other brain regions as well.
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DOI：
10.1073/pnas.0700293104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Armbruster, Blaine N.;Li, Xiang;Roth, Bryan L.
通讯作者：
Roth, Bryan L.
影响因子：
3.3
作者：
Ivanova, E.;Hwang, G. -S.;Pan, Z. -H.
通讯作者：
Pan, Z. -H.
影响因子：
2.5
作者：
Jones, Timothy A.;Leake, Patricia A.;Bonham, Ben
通讯作者：
Bonham, Ben
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H
影响因子：
8.8
作者：
Martersteck EM;Hirokawa KE;Evarts M;Bernard A;Duan X;Li Y;Ng L;Oh SW;Ouellette B;Royall JJ;Stoecklin M;Wang Q;Zeng H;Sanes JR;Harris JA
通讯作者：
Harris JA