Classes and Continua of Hippocampal CA1 Inhibitory Neurons Revealed by Single-Cell Transcriptomics Harris K, Hochgerner H, Skene NG, et al. PLoS Biol. 2018;16(6):e2006387. doi:10.1371/journal.pbio.2006387. Understanding any brain circuit will require a categorization of its constituent neurons. In hippocampal area CA1, at least 23 classes of GABAergic neurons have been proposed to date. However, this list may be incomplete; additionally, it is unclear whether discrete classes are sufficient to describe the diversity of cortical inhibitory neurons or whether continuous modes of variability are also required. We studied the transcriptomes of 3663 CA1 inhibitory cells, revealing 10 major GABAergic groups that divided into 49 fine-scale clusters. All previously described and several novel cell classes were identified, with 3 previously described classes unexpectedly found to be identical. A division into discrete classes, however, was not sufficient to describe the diversity of these cells, as continuous variation also occurred between and within classes. Latent factor analysis revealed that a single continuous variable could predict the expression levels of several genes, which correlated similarly with it across multiple cell types. Analysis of the genes correlating with this variable suggested it reflects a range from metabolically highly active faster-spiking cells that proximally target pyramidal cells to slower-spiking cells targeting distal dendrites or interneurons. These results elucidate the complexity of inhibitory neurons in one of the simplest cortical structures and show that characterizing these cells require continuous modes of variation as well as discrete cell classes.

中文翻译：

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抓住测序数据来考虑细胞和电路的复杂性。


单细胞转录组学揭示的海马 CA1 抑制神经元的类别和连续性 Harris K、Hochgerner H、Skene NG 等人。公共科学图书馆生物学。 2018;16(6):e2006387。 doi：10.1371/journal.pbio.2006387。了解任何大脑回路都需要对其组成神经元进行分类。在海马 CA1 区，迄今为止已提出至少 23 类 GABA 能神经元。然而，这个列表可能并不完整；此外，尚不清楚离散类别是否足以描述皮质抑制神经元的多样性，或者是否还需要连续的变异模式。我们研究了 3663 个 CA1 抑制细胞的转录组，揭示了 10 个主要的 GABA 能组，它们分为 49 个精细簇。所有之前描述的细胞类别和几个新的细胞类别都被鉴定出来，其中 3 个之前描述的类别出人意料地发现是相同的。然而，划分为离散的类并不足以描述这些细胞的多样性，因为类之间和类内也发生连续变化。潜在因素分析表明，单个连续变量可以预测多个基因的表达水平，这些基因在多种细胞类型中与其相关性类似。与该变量相关的基因分析表明，它反映了从近端靶向锥体细胞的代谢高度活跃的快速尖峰细胞到靶向远端树突或中间神经元的较慢尖峰细胞的范围。这些结果阐明了最简单的皮质结构之一中抑制性神经元的复杂性，并表明表征这些细胞需要连续的变异模式以及离散的细胞类别。