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A human-specific modifier of cortical circuit connectivity and function improves behavioral performance

Ewoud R.E. Schmidt, Hanzhi T. Zhao, Jung M. Park, Jacob B. Dahan, View ORCID ProfileChris C. Rodgers, Elizabeth M. C. Hillman, View ORCID ProfileRandy M. Bruno, View ORCID ProfileFranck Polleux
doi: https://doi.org/10.1101/852970
Ewoud R.E. Schmidt
1Department of Neuroscience, Columbia University, New York, NY 10032, USA
3Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10032, USA
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Hanzhi T. Zhao
2Department of Biomedical Engineering and Radiology, Columbia University, New York, NY 10032, USA
3Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10032, USA
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Jung M. Park
1Department of Neuroscience, Columbia University, New York, NY 10032, USA
3Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10032, USA
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Jacob B. Dahan
1Department of Neuroscience, Columbia University, New York, NY 10032, USA
3Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10032, USA
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Chris C. Rodgers
1Department of Neuroscience, Columbia University, New York, NY 10032, USA
3Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10032, USA
4Kavli Institute for Brain Science, Columbia University, New York, NY 10032, USA
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Elizabeth M. C. Hillman
2Department of Biomedical Engineering and Radiology, Columbia University, New York, NY 10032, USA
3Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10032, USA
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Randy M. Bruno
1Department of Neuroscience, Columbia University, New York, NY 10032, USA
3Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10032, USA
4Kavli Institute for Brain Science, Columbia University, New York, NY 10032, USA
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Franck Polleux
1Department of Neuroscience, Columbia University, New York, NY 10032, USA
3Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10032, USA
4Kavli Institute for Brain Science, Columbia University, New York, NY 10032, USA
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  • For correspondence: fp2304@columbia.edu
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SUMMARY

The remarkable cognitive abilities characterizing humans are thought to emerge from our unique features of cortical circuit architecture, including increased feedforward and feedback connectivity. However, our understanding of the evolutionary origin and nature of these changes in circuit connectivity, and how they impact cortical circuit function and behavior is currently lacking. Here, we demonstrate that expression of the human-specific gene duplication SRGAP2C leads to a specific increase in feedforward and feedback cortico-cortical connectivity. Moreover, humanized SRGAP2C mice display improved cortical sensory coding, and an enhanced ability to learn a cortex-dependent sensory discrimination task. Our results identify a novel substrate for human brain evolution whereby the emergence of SRGAP2C led to increased feedforward and feedback cortico-cortical connectivity, improved cortical sensory processing and enhanced behavioral performance.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • New Figure 6 and new authors (members of Randy Bruno's lab) and Supplemental files updated.

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 August 14, 2020.
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A human-specific modifier of cortical circuit connectivity and function improves behavioral performance
Ewoud R.E. Schmidt, Hanzhi T. Zhao, Jung M. Park, Jacob B. Dahan, Chris C. Rodgers, Elizabeth M. C. Hillman, Randy M. Bruno, Franck Polleux
bioRxiv 852970; doi: https://doi.org/10.1101/852970
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A human-specific modifier of cortical circuit connectivity and function improves behavioral performance
Ewoud R.E. Schmidt, Hanzhi T. Zhao, Jung M. Park, Jacob B. Dahan, Chris C. Rodgers, Elizabeth M. C. Hillman, Randy M. Bruno, Franck Polleux
bioRxiv 852970; doi: https://doi.org/10.1101/852970

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