Phenotypic variation of transcriptomic cell types in mouse motor cortex

Federico Scala, Dmitry Kobak, Matteo Bernabucci, Yves Bernaerts, Cathryn René Cadwell, Jesus Ramon Castro, Leonard Hartmanis, Xiaolong Jiang, Sophie Laturnus, Elanine Miranda, Shalaka Mulherkar, Zheng Huan Tan, Zizhen Yao, Hongkui Zeng, Rickard Sandberg, Philipp Berens () and Andreas S. Tolias ()
Additional contact information
Federico Scala: Baylor College of Medicine
Dmitry Kobak: University of Tübingen
Matteo Bernabucci: Baylor College of Medicine
Yves Bernaerts: University of Tübingen
Cathryn René Cadwell: University of California San Francisco
Jesus Ramon Castro: Baylor College of Medicine
Leonard Hartmanis: Karolinska Institutet
Xiaolong Jiang: Baylor College of Medicine
Sophie Laturnus: University of Tübingen
Elanine Miranda: Baylor College of Medicine
Shalaka Mulherkar: Baylor College of Medicine
Zheng Huan Tan: Baylor College of Medicine
Zizhen Yao: Allen Institute for Brain Science
Hongkui Zeng: Allen Institute for Brain Science
Rickard Sandberg: Karolinska Institutet
Philipp Berens: University of Tübingen
Andreas S. Tolias: Baylor College of Medicine

Nature, 2021, vol. 598, issue 7879, 144-150

Abstract: Abstract Cortical neurons exhibit extreme diversity in gene expression as well as in morphological and electrophysiological properties1,2. Most existing neural taxonomies are based on either transcriptomic3,4 or morpho-electric5,6 criteria, as it has been technically challenging to study both aspects of neuronal diversity in the same set of cells7. Here we used Patch-seq8 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.

Date: 2021
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DOI: 10.1038/s41586-020-2907-3

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