Center for Neuroscience and Artificial Intelligence, Baylor College of Medicine, Houston, TX, USA.
Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Nature. 2021 Oct;598(7879):144-150. doi: 10.1038/s41586-020-2907-3. Epub 2020 Nov 12.
Cortical neurons exhibit extreme diversity in gene expression as well as in morphological and electrophysiological properties. Most existing neural taxonomies are based on either transcriptomic or morpho-electric criteria, as it has been technically challenging to study both aspects of neuronal diversity in the same set of cells. Here we used Patch-seq to combine patch-clamp recording, biocytin staining, and single-cell RNA sequencing of more than 1,300 neurons in adult mouse primary motor cortex, providing a morpho-electric annotation of almost all transcriptomically defined neural cell types. We found that, although broad families of transcriptomic types (those expressing Vip, Pvalb, Sst and so on) had distinct and essentially non-overlapping morpho-electric phenotypes, individual transcriptomic types within the same family were not well separated in the morpho-electric space. Instead, there was a continuum of variability in morphology and electrophysiology, with neighbouring transcriptomic cell types showing similar morpho-electric features, often without clear boundaries between them. Our results suggest that neuronal types in the neocortex do not always form discrete entities. Instead, neurons form a hierarchy that consists of distinct non-overlapping branches at the level of families, but can form continuous and correlated transcriptomic and morpho-electrical landscapes within families.
皮质神经元在基因表达、形态和电生理特性方面表现出极大的多样性。大多数现有的神经分类法都是基于转录组或形态-电标准,因为在同一组细胞中同时研究神经元多样性的这两个方面在技术上具有挑战性。在这里,我们使用 Patch-seq 结合膜片钳记录、生物胞素染色和超过 1300 个成年小鼠初级运动皮层神经元的单细胞 RNA 测序,为几乎所有转录定义的神经细胞类型提供了形态-电注释。我们发现,尽管转录组类型的广泛家族(表达 Vip、Pvalb、Sst 等的类型)具有独特且本质上不重叠的形态-电表型,但同一家族内的单个转录组类型在形态-电空间中没有很好地区分开来。相反,形态和电生理学上存在着连续的可变性,相邻的转录组细胞类型具有相似的形态-电特征,通常没有明显的边界。我们的研究结果表明,新皮层中的神经元类型并不总是形成离散的实体。相反,神经元形成一个层次结构,在家族层面上由不同的不重叠分支组成,但在家族内部可以形成连续的、相关的转录组和形态-电景观。
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