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PLoS Biol. 2018 Jun 18;16(6):e2006387. doi: 10.1371/journal.pbio.2006387. eCollection 2018 Jun.

Classes and continua of hippocampal CA1 inhibitory neurons revealed by single-cell transcriptomics.

Author information

1
University College London Institute of Neurology, London, United Kingdom.
2
University College London Department of Neuroscience, Physiology and Pharmacology, London, United Kingdom.
3
Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
4
University College London Wolfson Institute for Biomedical Research, London, United Kingdom.
5
Department of Pharmacology, University of Oxford, Oxford, United Kingdom.

Abstract

Understanding any brain circuit will require a categorization of its constituent neurons. In hippocampal area CA1, at least 23 classes of GABAergic neuron 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 3,663 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 three 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 requires continuous modes of variation as well as discrete cell classes.

PMID:
29912866
PMCID:
PMC6029811
DOI:
10.1371/journal.pbio.2006387
[Indexed for MEDLINE]
Free PMC Article

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