Reconstruction of neocortex: Organelles, compartments, cells, circuits, and activity

doi:10.1016/j.cell.2022.01.023

Cell

Volume 185, Issue 6, 17 March 2022, Pages 1082-1100.e24

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https://doi.org/10.1016/j.cell.2022.01.023 Get rights and content

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Highlights

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A cortical reconstruction describes neuron connectivity, function, and cell biology
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Pyramidal areal synapse density appears invariant with distance from the soma
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Analysis of connectivity motifs reexamines "non-randomness" in cortical networks
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Pyramidal cells with more local connections give stronger and more reliable responses

Summary

We assembled a semi-automated reconstruction of L2/3 mouse primary visual cortex from ∼250 × 140 × 90 μm³ of electron microscopic images, including pyramidal and non-pyramidal neurons, astrocytes, microglia, oligodendrocytes and precursors, pericytes, vasculature, nuclei, mitochondria, and synapses. Visual responses of a subset of pyramidal cells are included. The data are publicly available, along with tools for programmatic and three-dimensional interactive access. Brief vignettes illustrate the breadth of potential applications relating structure to function in cortical circuits and neuronal cell biology. Mitochondria and synapse organization are characterized as a function of path length from the soma. Pyramidal connectivity motif frequencies are predicted accurately using a configuration model of random graphs. Pyramidal cells receiving more connections from nearby cells exhibit stronger and more reliable visual responses. Sample code shows data access and analysis.

Graphical abstract

Keywords

mouse, cortex, 3D reconstruction, electron microscopy, calcium imaging, pyramidal cell, mitochondria, synaptic connectivity, inhibitory cell, visual cortex

Data and code availability

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The EM image data, cellular segmentation, synapse segmentation, mitochondrion segmentation, and nucleus segmentation can be viewed at https://microns-explorer.org/phase1. The raw calcium imaging videos, light microscopy coregistration volume, visual stimulus, and calcium traces can be accessed via https://microns-explorer.org/phase1, and these are also available at https://github.com/seung-lab/MicronsBinder with the analysis code. Both the MicronsExplorer and MicronsBinder websites demonstrate how to access all intermediate analysis data (deposited as a Zenodo record).
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Along with the analysis code repository (https://github.com/seung-lab/MicronsBinder), the code for generating the cell and organelle reconstructions is available at https://github.com/seung-lab/.
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All original code has been deposited at Zenodo and is publicly available as of the date of publication. DOIs are listed in the key resources table.
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Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

¹⁶: These authors contributed equally

¹⁷: Senior author

¹⁸: Lead contact