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Sex, strain, and lateral differences in brain cytoarchitecture across a large mouse population

The mouse brain is by far the most intensively studied among mammalian brains, yet basic measures of its cytoarchitecture remain obscure. For example, quantifying cell numbers, and the interplay of sex, strain, and individual variability in cell density and volume is out of reach for many regions. T...

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Autores principales: Elkind, David, Hochgerner, Hannah, Aloni, Etay, Shental, Noam, Zeisel, Amit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10212558/
https://www.ncbi.nlm.nih.gov/pubmed/37144870
http://dx.doi.org/10.7554/eLife.82376
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author Elkind, David
Hochgerner, Hannah
Aloni, Etay
Shental, Noam
Zeisel, Amit
author_facet Elkind, David
Hochgerner, Hannah
Aloni, Etay
Shental, Noam
Zeisel, Amit
author_sort Elkind, David
collection PubMed
description The mouse brain is by far the most intensively studied among mammalian brains, yet basic measures of its cytoarchitecture remain obscure. For example, quantifying cell numbers, and the interplay of sex, strain, and individual variability in cell density and volume is out of reach for many regions. The Allen Mouse Brain Connectivity project produces high-resolution full brain images of hundreds of brains. Although these were created for a different purpose, they reveal details of neuroanatomy and cytoarchitecture. Here, we used this population to systematically characterize cell density and volume for each anatomical unit in the mouse brain. We developed a DNN-based segmentation pipeline that uses the autofluorescence intensities of images to segment cell nuclei even within the densest regions, such as the dentate gyrus. We applied our pipeline to 507 brains of males and females from C57BL/6J and FVB.CD1 strains. Globally, we found that increased overall brain volume does not result in uniform expansion across all regions. Moreover, region-specific density changes are often negatively correlated with the volume of the region; therefore, cell count does not scale linearly with volume. Many regions, including layer 2/3 across several cortical areas, showed distinct lateral bias. We identified strain-specific or sex-specific differences. For example, males tended to have more cells in extended amygdala and hypothalamic regions (MEA, BST, BLA, BMA, and LPO, AHN) while females had more cells in the orbital cortex (ORB). Yet, inter-individual variability was always greater than the effect size of a single qualifier. We provide the results of this analysis as an accessible resource for the community.
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spelling pubmed-102125582023-05-26 Sex, strain, and lateral differences in brain cytoarchitecture across a large mouse population Elkind, David Hochgerner, Hannah Aloni, Etay Shental, Noam Zeisel, Amit eLife Computational and Systems Biology The mouse brain is by far the most intensively studied among mammalian brains, yet basic measures of its cytoarchitecture remain obscure. For example, quantifying cell numbers, and the interplay of sex, strain, and individual variability in cell density and volume is out of reach for many regions. The Allen Mouse Brain Connectivity project produces high-resolution full brain images of hundreds of brains. Although these were created for a different purpose, they reveal details of neuroanatomy and cytoarchitecture. Here, we used this population to systematically characterize cell density and volume for each anatomical unit in the mouse brain. We developed a DNN-based segmentation pipeline that uses the autofluorescence intensities of images to segment cell nuclei even within the densest regions, such as the dentate gyrus. We applied our pipeline to 507 brains of males and females from C57BL/6J and FVB.CD1 strains. Globally, we found that increased overall brain volume does not result in uniform expansion across all regions. Moreover, region-specific density changes are often negatively correlated with the volume of the region; therefore, cell count does not scale linearly with volume. Many regions, including layer 2/3 across several cortical areas, showed distinct lateral bias. We identified strain-specific or sex-specific differences. For example, males tended to have more cells in extended amygdala and hypothalamic regions (MEA, BST, BLA, BMA, and LPO, AHN) while females had more cells in the orbital cortex (ORB). Yet, inter-individual variability was always greater than the effect size of a single qualifier. We provide the results of this analysis as an accessible resource for the community. eLife Sciences Publications, Ltd 2023-05-05 /pmc/articles/PMC10212558/ /pubmed/37144870 http://dx.doi.org/10.7554/eLife.82376 Text en © 2023, Elkind et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Computational and Systems Biology
Elkind, David
Hochgerner, Hannah
Aloni, Etay
Shental, Noam
Zeisel, Amit
Sex, strain, and lateral differences in brain cytoarchitecture across a large mouse population
title Sex, strain, and lateral differences in brain cytoarchitecture across a large mouse population
title_full Sex, strain, and lateral differences in brain cytoarchitecture across a large mouse population
title_fullStr Sex, strain, and lateral differences in brain cytoarchitecture across a large mouse population
title_full_unstemmed Sex, strain, and lateral differences in brain cytoarchitecture across a large mouse population
title_short Sex, strain, and lateral differences in brain cytoarchitecture across a large mouse population
title_sort sex, strain, and lateral differences in brain cytoarchitecture across a large mouse population
topic Computational and Systems Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10212558/
https://www.ncbi.nlm.nih.gov/pubmed/37144870
http://dx.doi.org/10.7554/eLife.82376
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