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A connectomic study of a petascale fragment of human cerebral cortex

View ORCID ProfileAlexander Shapson-Coe, View ORCID ProfileMichał Januszewski, View ORCID ProfileDaniel R. Berger, View ORCID ProfileArt Pope, View ORCID ProfileYuelong Wu, View ORCID ProfileTim Blakely, Richard L. Schalek, View ORCID ProfilePeter H. Li, Shuohong Wang, View ORCID ProfileJeremy Maitin-Shepard, View ORCID ProfileNeha Karlupia, View ORCID ProfileSven Dorkenwald, View ORCID ProfileEvelina Sjostedt, Laramie Leavitt, Dongil Lee, View ORCID ProfileLuke Bailey, View ORCID ProfileAngerica Fitzmaurice, View ORCID ProfileRohin Kar, View ORCID ProfileBenjamin Field, View ORCID ProfileHank Wu, View ORCID ProfileJulian Wagner-Carena, View ORCID ProfileDavid Aley, View ORCID ProfileJoanna Lau, View ORCID ProfileZudi Lin, View ORCID ProfileDonglai Wei, View ORCID ProfileHanspeter Pfister, Adi Peleg, View ORCID ProfileViren Jain, View ORCID ProfileJeff W. Lichtman
doi: https://doi.org/10.1101/2021.05.29.446289
Alexander Shapson-Coe
1Dept. of Molecular and Cellular Biology, Center for Brain Science, Harvard U., Cambridge, MA
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Michał Januszewski
2Google Research, Zürich, Switzerland
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Daniel R. Berger
1Dept. of Molecular and Cellular Biology, Center for Brain Science, Harvard U., Cambridge, MA
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Art Pope
3Google Research, Mountain View, CA
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Yuelong Wu
1Dept. of Molecular and Cellular Biology, Center for Brain Science, Harvard U., Cambridge, MA
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Tim Blakely
4Google Research, Seattle, WA
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Richard L. Schalek
1Dept. of Molecular and Cellular Biology, Center for Brain Science, Harvard U., Cambridge, MA
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Peter H. Li
3Google Research, Mountain View, CA
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Shuohong Wang
1Dept. of Molecular and Cellular Biology, Center for Brain Science, Harvard U., Cambridge, MA
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Jeremy Maitin-Shepard
3Google Research, Mountain View, CA
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Neha Karlupia
1Dept. of Molecular and Cellular Biology, Center for Brain Science, Harvard U., Cambridge, MA
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Sven Dorkenwald
3Google Research, Mountain View, CA
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Evelina Sjostedt
1Dept. of Molecular and Cellular Biology, Center for Brain Science, Harvard U., Cambridge, MA
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Laramie Leavitt
3Google Research, Mountain View, CA
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Dongil Lee
1Dept. of Molecular and Cellular Biology, Center for Brain Science, Harvard U., Cambridge, MA
5Dept. of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Korea
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Luke Bailey
1Dept. of Molecular and Cellular Biology, Center for Brain Science, Harvard U., Cambridge, MA
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Angerica Fitzmaurice
1Dept. of Molecular and Cellular Biology, Center for Brain Science, Harvard U., Cambridge, MA
6Northeastern University
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Rohin Kar
1Dept. of Molecular and Cellular Biology, Center for Brain Science, Harvard U., Cambridge, MA
6Northeastern University
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Benjamin Field
1Dept. of Molecular and Cellular Biology, Center for Brain Science, Harvard U., Cambridge, MA
6Northeastern University
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Hank Wu
1Dept. of Molecular and Cellular Biology, Center for Brain Science, Harvard U., Cambridge, MA
6Northeastern University
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Julian Wagner-Carena
1Dept. of Molecular and Cellular Biology, Center for Brain Science, Harvard U., Cambridge, MA
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David Aley
1Dept. of Molecular and Cellular Biology, Center for Brain Science, Harvard U., Cambridge, MA
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Joanna Lau
1Dept. of Molecular and Cellular Biology, Center for Brain Science, Harvard U., Cambridge, MA
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Zudi Lin
7School of Engineering and Applied Sciences, Harvard U., Cambridge, MA
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Donglai Wei
7School of Engineering and Applied Sciences, Harvard U., Cambridge, MA
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Hanspeter Pfister
7School of Engineering and Applied Sciences, Harvard U., Cambridge, MA
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Adi Peleg
1Dept. of Molecular and Cellular Biology, Center for Brain Science, Harvard U., Cambridge, MA
8Google, Cambridge, MA
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Viren Jain
3Google Research, Mountain View, CA
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  • For correspondence: jeff@mcb.harvard.edu viren@google.com
Jeff W. Lichtman
1Dept. of Molecular and Cellular Biology, Center for Brain Science, Harvard U., Cambridge, MA
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  • For correspondence: jeff@mcb.harvard.edu viren@google.com
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Abstract

We acquired a rapidly preserved human surgical sample from the temporal lobe of the cerebral cortex. We stained a 1 mm3 volume with heavy metals, embedded it in resin, cut more than 5000 slices at ∼30 nm and imaged these sections using a high-speed multibeam scanning electron microscope. We used computational methods to render the three-dimensional structure containing 57,216 cells, hundreds of millions of neurites and 133.7 million synaptic connections. The 1.4 petabyte electron microscopy volume, the segmented cells, cell parts, blood vessels, myelin, inhibitory and excitatory synapses, and 104 manually proofread cells are available to peruse online. Many interesting and unusual features were evident in this dataset. Glia outnumbered neurons 2:1 and oligodendrocytes were the most common cell type in the volume. Excitatory spiny neurons comprised 69% of the neuronal population, and excitatory synapses also were in the majority (76%). The synaptic drive onto spiny neurons was biased more strongly toward excitation (70%) than was the case for inhibitory interneurons (48%). Despite incompleteness of the automated segmentation caused by split and merge errors, we could automatically generate (and then validate) connections between most of the excitatory and inhibitory neuron types both within and between layers. In studying these neurons we found that deep layer excitatory cell types can be classified into new subsets, based on structural and connectivity differences, and that chandelier interneurons not only innervate excitatory neuron initial segments as previously described, but also each other’s initial segments. Furthermore, among the thousands of weak connections established on each neuron, there exist rarer highly powerful axonal inputs that establish multi-synaptic contacts (up to ∼20 synapses) with target neurons. Our analysis indicates that these strong inputs are specific, and allow small numbers of axons to have an outsized role in the activity of some of their postsynaptic partners.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://h01-release.storage.googleapis.com/landing.html

  • https://github.com/google/neuroglancer

  • https://github.com/ashapsoncoe/CREST

  • https://github.com/ashapsoncoe/h01

  • https://storage.googleapis.com/h01-release/data/20210601/svg/connections_I.svg

  • https://storage.googleapis.com/h01-release/data/20210601/svg/connections_E.svg

  • https://www.youtube.com/watch?v=g5r3OcChnRg&feature=youtu.be

  • https://www.youtube.com/watch?v=vg2wT_36jmA&feature=youtu.be

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 25, 2021.
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A connectomic study of a petascale fragment of human cerebral cortex
Alexander Shapson-Coe, Michał Januszewski, Daniel R. Berger, Art Pope, Yuelong Wu, Tim Blakely, Richard L. Schalek, Peter H. Li, Shuohong Wang, Jeremy Maitin-Shepard, Neha Karlupia, Sven Dorkenwald, Evelina Sjostedt, Laramie Leavitt, Dongil Lee, Luke Bailey, Angerica Fitzmaurice, Rohin Kar, Benjamin Field, Hank Wu, Julian Wagner-Carena, David Aley, Joanna Lau, Zudi Lin, Donglai Wei, Hanspeter Pfister, Adi Peleg, Viren Jain, Jeff W. Lichtman
bioRxiv 2021.05.29.446289; doi: https://doi.org/10.1101/2021.05.29.446289
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A connectomic study of a petascale fragment of human cerebral cortex
Alexander Shapson-Coe, Michał Januszewski, Daniel R. Berger, Art Pope, Yuelong Wu, Tim Blakely, Richard L. Schalek, Peter H. Li, Shuohong Wang, Jeremy Maitin-Shepard, Neha Karlupia, Sven Dorkenwald, Evelina Sjostedt, Laramie Leavitt, Dongil Lee, Luke Bailey, Angerica Fitzmaurice, Rohin Kar, Benjamin Field, Hank Wu, Julian Wagner-Carena, David Aley, Joanna Lau, Zudi Lin, Donglai Wei, Hanspeter Pfister, Adi Peleg, Viren Jain, Jeff W. Lichtman
bioRxiv 2021.05.29.446289; doi: https://doi.org/10.1101/2021.05.29.446289

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