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Temporally matched subpopulations of selectively interconnected principal neurons in the hippocampus

Nature Neuroscience volume 14, pages 495–504 (2011)Cite this article

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Abstract

The extent to which individual neurons are interconnected selectively within brain circuits is an unresolved problem in neuroscience. Neurons can be organized into preferentially interconnected microcircuits, but whether this reflects genetically defined subpopulations is unclear. We found that the principal neurons in the main subdivisions of the hippocampus consist of distinct subpopulations that are generated during distinct time windows and that interconnect selectively across subdivisions. In two mouse lines in which transgene expression was driven by the neuron-specific Thy1 promoter, transgene expression allowed us to visualize distinct populations of principal neurons with unique and matched patterns of gene expression, shared distinct neurogenesis and synaptogenesis time windows, and selective connectivity at dentate gyrus-CA3 and CA3-CA1 synapses. Matched subpopulation marker genes and neuronal subtype markers mapped near clusters of olfactory receptor genes. The nonoverlapping matched timings of synaptogenesis accounted for the selective connectivities of these neurons in CA3. Therefore, the hippocampus contains parallel connectivity channels assembled from distinct principal neuron subpopulations through matched schedules of synaptogenesis.

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Figure 1: Distinct transcriptomes of Lsi1 and Lsi2 hippocampal principal neurons.
Figure 2: Detection of Lsi1 and Lsi2 precursors and neurons during hippocampal development.
Figure 3: Temporal windows of Lsi1 and Lsi2 neurogenesis during hippocampal development.
Figure 4: Transcripts shared among Lsi1 or Lsi2 subpopulations in dentate gyrus, CA3 and CA1.
Figure 5: Distinct and matched synaptogenesis schedules by Lsi1 and Lsi2 subpopulations.
Figure 6: Selective connectivity between matched granule cells and CA3 pyramidal neuron subpopulations.
Figure 7: Selective connectivity between matched CA3 and CA1 pyramidal neuron subpopulations.
Figure 8: Influence of synaptogenesis timing and subpopulation identity on selective connectivity.

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Acknowledgements

We thank S. Arber, A. Lüthi and B. Roska (Friedrich Miescher Institute; FMI) for comments on the manuscript, C. Genoud (FMI) for assistance with immuno-electron microscopy, M. Wiechert and A. Ponti (FMI) for data analysis assistance, and S. Arber for the rabies-mCherry virus. The FMI is part of the Novartis Research Foundation.

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  1. Yuichi Deguchi, Flavio Donato and Ivan Galimberti: These authors contributed equally to this work.

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  1. Friedrich Miescher Institute, Basel, Switzerland

    Yuichi Deguchi, Flavio Donato, Ivan Galimberti, Erik Cabuy & Pico Caroni

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  1. Yuichi Deguchi
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Contributions

Y.D. conceived and carried out the gene expression and the adult subpopulation mapping analysis. F.D. conceived and carried out the neurogenesis and synaptogenesis analysis and parts of the electron microscopy and connectivity analysis. I.G. conceived and carried out most of the connectivity analysis. E.C. carried out and optimized the cell genomics experiments. P.C. helped devise the experiments and wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to Pico Caroni.

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Deguchi, Y., Donato, F., Galimberti, I. et al. Temporally matched subpopulations of selectively interconnected principal neurons in the hippocampus. Nat Neurosci 14, 495–504 (2011). https://doi.org/10.1038/nn.2768

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