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Molecular organization of CA1 interneuron classes

Kenneth D. Harris, Lorenza Magno, Linda Katona, Peter Lönnerberg, Ana B. Muñoz Manchado, Peter Somogyi, Nicoletta Kessaris, Sten Linnarsson, Jens Hjerling-Leffler
doi: https://doi.org/10.1101/034595
Kenneth D. Harris
1UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
2UCL Department of Neuroscience, Physiology and Pharmacology, 21 University Street, London WC1E 6DE, UK
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Lorenza Magno
3Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
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Linda Katona
5MRC Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3TH, UK
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Peter Lönnerberg
4Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden
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Ana B. Muñoz Manchado
4Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden
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Peter Somogyi
5MRC Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3TH, UK
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Nicoletta Kessaris
3Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
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Sten Linnarsson
4Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden
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Jens Hjerling-Leffler
4Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden
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Abstract

GABAergic interneurons are key regulators of hippocampal circuits, but our understanding of the diversity and classification of these cells remains controversial. Here we analyze the organization of interneurons in the CA1 area, using the combinatorial patterns of gene expression revealed by single-cell mRNA sequencing (scRNA-seq). This analysis reveals a 5-level hierarchy of cell classes. Most of the predicted classes correspond closely to known interneuron types, allowing us to predict a large number of novel molecular markers of these classes. In addition we identified a major new interneuron population localized at the border of strata radiatum and lacunosum-moleculare that we term “R2C2 cells” after their characteristic combinatorial expression of Rgs12, Reln, Cxcl14, and Cpne5. Several predictions of this classification scheme were verified using in situ hybridization and immunohistochemistry, providing further confidence in the gene expression patterns and novel classes predicted by the single cell data.

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Posted December 16, 2015.
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Molecular organization of CA1 interneuron classes
Kenneth D. Harris, Lorenza Magno, Linda Katona, Peter Lönnerberg, Ana B. Muñoz Manchado, Peter Somogyi, Nicoletta Kessaris, Sten Linnarsson, Jens Hjerling-Leffler
bioRxiv 034595; doi: https://doi.org/10.1101/034595
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Molecular organization of CA1 interneuron classes
Kenneth D. Harris, Lorenza Magno, Linda Katona, Peter Lönnerberg, Ana B. Muñoz Manchado, Peter Somogyi, Nicoletta Kessaris, Sten Linnarsson, Jens Hjerling-Leffler
bioRxiv 034595; doi: https://doi.org/10.1101/034595

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