Extensive and spatially variable within-cell-type heterogeneity across the basolateral amygdala
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).
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Discrete and continuous heterogeneity in the basolateral amygdalaNCBI Gene Expression Omnibus, GSE148866.
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BLA heterpgeneityFigShare, doi:10.6084/m9.figshare.c.5108165.
Article and author information
Author details
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.
Reviewing Editor
- Anne E West, Duke University School of Medicine, United States
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).
Version history
- Received: May 16, 2020
- Accepted: August 26, 2020
- Accepted Manuscript published: September 1, 2020 (version 1)
- 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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