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Regional, layer, and cell-class specific connectivity of the mouse default mode network

View ORCID ProfileJennifer D. Whitesell, Adam Liska, Ludovico Coletta, Karla E. Hirokawa, Phillip Bohn, Ali Williford, View ORCID ProfilePeter A. Groblewski, Nile Graddis, Leonard Kuan, View ORCID ProfileJoseph E. Knox, Anh Ho, Wayne Wakeman, View ORCID ProfilePhilip R. Nicovich, View ORCID ProfileThuc Nghi Nguyen, Emma Garren, Cindy T. J. van Velthoven, Olivia Fong, View ORCID ProfileDavid Feng, Maitham Naeemi, Alex M. Henry, View ORCID ProfileNick Dee, View ORCID ProfileKimberly A. Smith, Boaz P. Levi, View ORCID ProfileLydia Ng, View ORCID ProfileBosiljka Tasic, View ORCID ProfileHongkui Zeng, View ORCID ProfileStefan Mihalas, View ORCID ProfileAlessandro Gozzi, Julie A. Harris
doi: https://doi.org/10.1101/2020.05.13.094458
Jennifer D. Whitesell
1Allen Institute for Brain Science, Seattle, WA
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Adam Liska
2Functional Neuroimaging Laboratory, Istituto Italiano di Tecnologia, Center for Neuroscience and Cognitive Systems @ UniTn, Rovereto, Italy
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Ludovico Coletta
2Functional Neuroimaging Laboratory, Istituto Italiano di Tecnologia, Center for Neuroscience and Cognitive Systems @ UniTn, Rovereto, Italy
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Karla E. Hirokawa
1Allen Institute for Brain Science, Seattle, WA
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Phillip Bohn
1Allen Institute for Brain Science, Seattle, WA
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Ali Williford
1Allen Institute for Brain Science, Seattle, WA
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Peter A. Groblewski
1Allen Institute for Brain Science, Seattle, WA
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Nile Graddis
1Allen Institute for Brain Science, Seattle, WA
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Leonard Kuan
1Allen Institute for Brain Science, Seattle, WA
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Joseph E. Knox
1Allen Institute for Brain Science, Seattle, WA
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Anh Ho
1Allen Institute for Brain Science, Seattle, WA
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Wayne Wakeman
1Allen Institute for Brain Science, Seattle, WA
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Philip R. Nicovich
1Allen Institute for Brain Science, Seattle, WA
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Thuc Nghi Nguyen
1Allen Institute for Brain Science, Seattle, WA
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Emma Garren
1Allen Institute for Brain Science, Seattle, WA
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Cindy T. J. van Velthoven
1Allen Institute for Brain Science, Seattle, WA
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Olivia Fong
1Allen Institute for Brain Science, Seattle, WA
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David Feng
1Allen Institute for Brain Science, Seattle, WA
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Maitham Naeemi
1Allen Institute for Brain Science, Seattle, WA
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Alex M. Henry
1Allen Institute for Brain Science, Seattle, WA
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Nick Dee
1Allen Institute for Brain Science, Seattle, WA
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Kimberly A. Smith
1Allen Institute for Brain Science, Seattle, WA
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Boaz P. Levi
1Allen Institute for Brain Science, Seattle, WA
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Lydia Ng
1Allen Institute for Brain Science, Seattle, WA
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Bosiljka Tasic
1Allen Institute for Brain Science, Seattle, WA
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Hongkui Zeng
1Allen Institute for Brain Science, Seattle, WA
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Stefan Mihalas
1Allen Institute for Brain Science, Seattle, WA
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Alessandro Gozzi
2Functional Neuroimaging Laboratory, Istituto Italiano di Tecnologia, Center for Neuroscience and Cognitive Systems @ UniTn, Rovereto, Italy
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Julie A. Harris
1Allen Institute for Brain Science, Seattle, WA
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  • For correspondence: julieha@alleninstitute.org
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Abstract

The evolutionarily conserved default mode network (DMN) is characterized by temporally correlated activity between brain regions during resting states. The DMN has emerged as a selectively vulnerable network in multiple disorders, so understanding its anatomical composition will provide fundamental insight into how its function is impacted by disease. Reproducible rodent analogs of the human DMN offer an opportunity to investigate the underlying brain regions and structural connectivity (SC) with high spatial and cell type resolution. Here, we performed systematic analyses using mouse resting state functional magnetic resonance imaging to identify the DMN and whole brain axonal tracing data, co-registered to the 3D Allen Mouse Common Coordinate Framework reference atlas. We identified the specific, predominantly cortical, brain regions comprising the mouse DMN and report preferential SC between these regions. Next, at the cell class level, we report that cortical layer (L) 2/3 neurons in DMN regions project almost exclusively to other DMN regions, whereas L5 neurons project to targets both in and out of the DMN. We then test the hypothesis that in- and out-DMN projection patterns originate from distinct L5 neuron sub-classes using an intersectional viral tracing strategy to label all the axons from neurons defined by a single target. In the ventral retrosplenial cortex, a core DMN region, we found two L5 projection types related to the DMN and mapped them to unique transcriptomically-defined cell types. Together, our results provide a multi-scale description of the anatomical correlates of the mouse DMN.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • http://connectivity.brain-map.org/

  • https://doi.org/10.17632/7y6xr753g4.1

  • https://doi.org/10.17632/r2w865c959.1

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 14, 2020.
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Regional, layer, and cell-class specific connectivity of the mouse default mode network
Jennifer D. Whitesell, Adam Liska, Ludovico Coletta, Karla E. Hirokawa, Phillip Bohn, Ali Williford, Peter A. Groblewski, Nile Graddis, Leonard Kuan, Joseph E. Knox, Anh Ho, Wayne Wakeman, Philip R. Nicovich, Thuc Nghi Nguyen, Emma Garren, Cindy T. J. van Velthoven, Olivia Fong, David Feng, Maitham Naeemi, Alex M. Henry, Nick Dee, Kimberly A. Smith, Boaz P. Levi, Lydia Ng, Bosiljka Tasic, Hongkui Zeng, Stefan Mihalas, Alessandro Gozzi, Julie A. Harris
bioRxiv 2020.05.13.094458; doi: https://doi.org/10.1101/2020.05.13.094458
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Regional, layer, and cell-class specific connectivity of the mouse default mode network
Jennifer D. Whitesell, Adam Liska, Ludovico Coletta, Karla E. Hirokawa, Phillip Bohn, Ali Williford, Peter A. Groblewski, Nile Graddis, Leonard Kuan, Joseph E. Knox, Anh Ho, Wayne Wakeman, Philip R. Nicovich, Thuc Nghi Nguyen, Emma Garren, Cindy T. J. van Velthoven, Olivia Fong, David Feng, Maitham Naeemi, Alex M. Henry, Nick Dee, Kimberly A. Smith, Boaz P. Levi, Lydia Ng, Bosiljka Tasic, Hongkui Zeng, Stefan Mihalas, Alessandro Gozzi, Julie A. Harris
bioRxiv 2020.05.13.094458; doi: https://doi.org/10.1101/2020.05.13.094458

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