Cell type composition and circuit organization of clonally related excitatory neurons in the juvenile mouse neocortex
- University of California, San Francisco, United States
- Baylor College of Medicine, United States
- University of Tübingen, Germany
- Karolinska Institutet, Sweden
Abstract
Clones of excitatory neurons derived from a common progenitor have been proposed to serve as elementary information processing modules in the neocortex. To characterize the cell types and circuit diagram of clonally related neurons, we performed multi-cell patch clamp recordings and Patch-seq on neurons derived from Nestin-positive progenitors labeled by tamoxifen induction at embryonic day 10.5. The resulting clones are derived from two radial glia on average, span cortical layers 2-6, and are composed of a random sampling of transcriptomic cell types. We find an interaction between shared lineage and connectivity: related neurons are more likely to be connected vertically across cortical layers, but not laterally within the same layer. These findings challenge the view that related neurons show uniformly increased connectivity and suggest that integration of vertical intra-clonal input with lateral inter-clonal input may represent a developmentally programmed connectivity motif supporting the emergence of functional circuits.
Data availability
Sequencing data have been deposited in GEO under accession code GSE140946. All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2, 3 and 4. The source data provided for Figure 4 also apply to Figure 5 and Table 1.
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Cell type composition and circuit organization of neocortical radial clonesNCBI Gene Expression Omnibus, GSE140946.
Article and author information
Author details
Kimberley F Tolias
Andreas Savas Tolias
Funding
Baylor College of Medicine (Optical Imaging and Vital Microscopy Core)
- Andreas Savas Tolias
Baylor College of Medicine (Faculty start-up fund)
- Xiaolong Jiang
National Institutes of Health (F30MH095440,T32GM007330)
- Cathryn R Cadwell
National Institutes of Health (F30MH112312)
- Paul G Fahey
Baylor Research Advocates for Student Scientists (BRASS Scholar Award)
- Cathryn R Cadwell
- Paul G Fahey
National Institutes of Health (R01MH103108,R01DA028525,DP1EY023176,P30EY002520,T32EY07001,DP1OD008301)
- Andreas Savas Tolias
National Science Foundation (707359)
- Andreas Savas Tolias
Svenska Forskningsrådet Formas
- Rickard Sandberg
Vallee Foundation
- Rickard Sandberg
Deutsche Forschungsgemeinschaft (EXC 2064,BE5601/4-1)
- Philipp Berens
Bundesministerium für Bildung und Forschung (FKZ 01GQ1601)
- Philipp Berens
McKnight Foundation (McKnight Scholar Award)
- Andreas Savas Tolias
Arnold and Mabel Beckman Foundation (Young Investigator Award)
- Andreas Savas Tolias
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Anne E West, Duke University School of Medicine, United States
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to an approved institutional animal care and use committee (IACUC) protocol of Baylor College of Medicine (protocol # AN-4703). Every effort was made to minimize suffering.
Version history
- Received: October 22, 2019
- Accepted: March 2, 2020
- Accepted Manuscript published: March 5, 2020 (version 1)
- Accepted Manuscript updated: March 6, 2020 (version 2)
- Version of Record published: April 16, 2020 (version 3)
Copyright
© 2020, Cadwell et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cell type composition and circuit organization of clonally related excitatory neurons in the juvenile mouse neocortex
eLife 9:e52951.
https://doi.org/10.7554/eLife.52951
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