Sex, strain and lateral differences in brain cytoarchitecture across a large mouse population
- Open University of Israel, Israel
- Technion - Israel Institute of Technology, Israel
Abstract
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 deep neural network-based segmentation pipeline that uses the auto-fluorescence 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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Tables related to values of data appear in the figures can be found in excel file.
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A mesoscale connectome of the mouse brainAllen Brain Institute API.
Article and author information
Author details
Funding
European Research Council (TYPEWIRE-852786)
- Hannah Hochgerner
- Etay Aloni
- Amit Zeisel
Human Frontier Science Program (CDA-0039/2019-C)
- Hannah Hochgerner
- Amit Zeisel
Israel Science Foundation (2028912)
- Hannah Hochgerner
- Amit Zeisel
Swedish Brain Foundation
- Hannah Hochgerner
Israel ministry of science, technology & space (3-16033)
- Noam Shental
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Elkind 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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Sex, strain and lateral differences in brain cytoarchitecture across a large mouse population
eLife 12:e82376.
https://doi.org/10.7554/eLife.82376
