1. Neuroscience
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Extensive and spatially variable within-cell-type heterogeneity across the basolateral amygdala

  1. Timothy P O'Leary
  2. Kaitlin E Sullivan
  3. Lihua Wang
  4. Jody Clements
  5. Andrew L Lemire
  6. Mark S Cembrowski  Is a corresponding author
  1. University of British Columbia, Canada
  2. Janelia Research Campus, Howard Hughes Medical Institute, United States
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Cite this article as: eLife 2020;9:e59003 doi: 10.7554/eLife.59003

Abstract

The basolateral amygdala complex (BLA), extensively connected with both local amygdalar nuclei as well as long-range circuits, is involved in a diverse array of functional roles. Understanding the mechanisms of such functional diversity will be greatly informed by understanding the cell-type-specific landscape of the BLA. Here, beginning with single-cell RNA sequencing, we identified both discrete and graded continuous gene-expression differences within the mouse BLA. Via in situ hybridization, we next mapped this discrete transcriptomic heterogeneity onto a sharp spatial border between the basal and lateral amygdala nuclei, and identified continuous spatial gene-expression gradients within each of these regions. These discrete and continuous spatial transformations of transcriptomic cell-type identity were recapitulated by local morphology as well as long-range connectivity. Thus, BLA excitatory neurons are a highly heterogenous collection of neurons that spatially covary in molecular, cellular, and circuit properties. This heterogeneity likely drives pronounced spatial variation in BLA computation and function.

Data availability

Raw and processed scRNA-seq datasets have been deposited in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus under GEO: GSE148866.Data underlying the results of this manuscript have been provided on FigShare (doi:10.6084/m9.figshare.c.5108165).

The following data sets were generated
    1. Sullivan K
    2. Cembrowski M
    (2020) BLA heterpgeneity
    FigShare, doi:10.6084/m9.figshare.c.5108165.

Article and author information

Author details

  1. Timothy P O'Leary

    Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Kaitlin E Sullivan

    Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Lihua Wang

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jody Clements

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Andrew L Lemire

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Mark S Cembrowski

    Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada
    For correspondence
    mark.cembrowski@ubc.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8275-7362

Funding

Natural Sciences and Engineering Research Council of Canada (RGPIN-2019-04507)

  • Mark S Cembrowski

Canadian Institutes of Health Research (PJT-419798)

  • Mark S Cembrowski

Canadian Foundation for Innovation (John R. Evans Leaders Fund 38369)

  • Mark S Cembrowski

University of British Columbia

  • Mark S Cembrowski

Howard Hughes Medical Institute

  • Mark S Cembrowski

Michael Smith Foundation for Health Research (SCH-2020-0383)

  • Mark S Cembrowski

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Experimental procedures were approved by the Animal Care Committee at the University of British Columbia (A18-0267; A18-0285) and the Institutional Animal Care and Use Committee at the Janelia Research Campus (11-78).

Reviewing Editor

  1. Anne E West, Duke University School of Medicine, United States

Publication history

  1. Received: May 16, 2020
  2. Accepted: August 26, 2020
  3. Accepted Manuscript published: September 1, 2020 (version 1)
  4. Version of Record published: September 11, 2020 (version 2)

Copyright

© 2020, O'Leary et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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