CA1 pyramidal cell diversity is rootedin the time of neurogenesis
- INSERM Aix-Marseille University, France
- Newcastle University, United Kingdom
- King's College London, United Kingdom
- French Institute of Health and Medical Research, France
Abstract
Cellular diversity supports the computational capacity and flexibility of cortical circuits. Accordingly, principal neurons at the CA1 output node of the murine hippocampus are increasingly recognized as a heterogeneous population. Their genes, molecular content, intrinsic morphophysiology, connectivity, and function seem to segregate along the main anatomical axes of the hippocampus. Since these axes reflect the temporal order of principal cell neurogenesis, we directly examined the relationship between birthdate and CA1 pyramidal neuron diversity, focusing on the ventral hippocampus. We used a genetic fate-mapping approach that allowed tagging three groups of age-matched principal neurons: pioneer, early- and late-born. Using a combination of neuroanatomy, slice physiology, connectivity tracing and cFos staining in mice, we show that birthdate is a strong predictor of CA1 principal cell diversity. We unravel a subpopulation of pioneer neurons recruited in familiar environments with remarkable positioning, morpho-physiological features, and connectivity. Therefore, despite the expected plasticity of hippocampal circuits, given their role in learning and memory, the diversity of their main components is also partly determined at the earliest steps of development.
Data availability
Data generated or analysed during this study are included in the manuscript or available on Dryad (doi:10.5061/dryad.76hdr7swh). A single source data file (multiple sheets) is included in the submission. Raw data and code from the following experiments are also included in the submission: ex vivo electrophysiology. All other data and codes will be made public as soon as possible and are available upon request.
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Whole-cell current clamp recordings in sliceDryad Digital Repository, doi:10.5061/dryad.76hdr7swh.
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Anti-cfos immunostaining after explorationDryad Digital Repository, doi:10.5061/dryad.280gb5mq2.
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Exploration data for cfos expression analysisDryad Digital Repository, doi:10.5061/dryad.7d7wm37v2.
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Whole-cell voltage clamp recordings in sliceDryad Digital Repository, doi:10.5061/dryad.r4xgxd2cf.
Article and author information
Author details
Funding
H2020 European Research Council (646925)
- Rosa Cossart
Agence Nationale de la Recherche (ANR-13-ISV40002-01)
- Rosa Cossart
Agence Nationale de la Recherche (JTC-2017-021)
- Rosa Cossart
Fondation Bettencourt Schueller (Prix des Sciences de la Vie)
- Rosa Cossart
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All protocols were performed under the guidelines of the French National Ethics Committee for Sciencesand Health report on "Ethical Principles for Animal Experimentation" in agreement with theEuropean Community Directive 86/609/EEC under agreement #01 413.03. All efforts were madeto minimize pain and suffering and to reduce the number of animals used.
Copyright
© 2021, Cavalieri 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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CA1 pyramidal cell diversity is rootedin the time of neurogenesis
eLife 10:e69270.
https://doi.org/10.7554/eLife.69270
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