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High-throughput sequencing of macaque basolateral amygdala projections reveals dissociable connectional motifs with frontal cortex

View ORCID ProfileZachary R Zeisler, Liza London, William G Janssen, J Megan Fredericks, Catherine Elorette, Atsushi Fujimoto, Huiqing Zhan, Brian E Russ, Roger L Clem, Patrick R Hof, Frederic M Stoll, Peter H Rudebeck
doi: https://doi.org/10.1101/2023.01.18.524407
Zachary R Zeisler
1Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029
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  • ORCID record for Zachary R Zeisler
Liza London
1Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029
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William G Janssen
1Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029
2Microscopy and Advanced Bioimaging CoRE, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029
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J Megan Fredericks
1Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029
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Catherine Elorette
1Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029
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Atsushi Fujimoto
1Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029
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Huiqing Zhan
5Cold Spring Harbor Laboratory, 1 Bungtown Rd, Syosset, NY 11791
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Brian E Russ
1Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029
3Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute, 140 Old Orangeburg Road, 10 Orangeburg, NY 10962
4Department of Psychiatry, New York University at Langone, One, 8 Park Ave, New York, NY 10016
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Roger L Clem
1Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029
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Patrick R Hof
1Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029
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Frederic M Stoll
1Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029
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Peter H Rudebeck
1Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029
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  • For correspondence: peter.rudebeck@mssm.edu
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Abstract

The basolateral amygdala (BLA) projects widely across the macaque frontal cortex1–4, and amygdalo-frontal projections are critical for optimal emotional responding5 and decision-making6. Yet, little is known about the single-neuron architecture of these projections: namely, whether single BLA neurons project to multiple parts of the frontal cortex. Here, we use MAPseq7 to determine the projection patterns of over 3000 macaque BLA neurons. We found that one-third of BLA neurons have two or more distinct targets in parts of frontal cortex and of subcortical structures. Further, we reveal non-random structure within these branching patterns such that neurons with four targets are more frequently observed than those with two or three, indicative of widespread networks. Consequently, these multi-target single neurons form distinct networks within medial and ventral frontal cortex consistent with their known functions in regulating mood and decision-making. Additionally, we show that branching patterns of single neurons shape functional networks in the brain as assessed by fMRI-based functional connectivity. These results provide a neuroanatomical basis for the role of the BLA in coordinating brain-wide responses to valent stimuli8 and highlight the importance of high-resolution neuroanatomical data for understanding functional networks in the brain.

Competing Interest Statement

The authors have declared no competing interest.

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 January 18, 2023.
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High-throughput sequencing of macaque basolateral amygdala projections reveals dissociable connectional motifs with frontal cortex
Zachary R Zeisler, Liza London, William G Janssen, J Megan Fredericks, Catherine Elorette, Atsushi Fujimoto, Huiqing Zhan, Brian E Russ, Roger L Clem, Patrick R Hof, Frederic M Stoll, Peter H Rudebeck
bioRxiv 2023.01.18.524407; doi: https://doi.org/10.1101/2023.01.18.524407
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High-throughput sequencing of macaque basolateral amygdala projections reveals dissociable connectional motifs with frontal cortex
Zachary R Zeisler, Liza London, William G Janssen, J Megan Fredericks, Catherine Elorette, Atsushi Fujimoto, Huiqing Zhan, Brian E Russ, Roger L Clem, Patrick R Hof, Frederic M Stoll, Peter H Rudebeck
bioRxiv 2023.01.18.524407; doi: https://doi.org/10.1101/2023.01.18.524407

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