epDevAtlas: Mapping GABAergic cells and microglia in postnatal mouse brains

Abstract

During development, brain regions follow encoded growth trajectories. Compared to classical brain growth charts, high-definition growth charts could quantify regional volumetric growth and constituent cell types, improving our understanding of typical and pathological brain development. Here, we create high-resolution 3D atlases of the early postnatal mouse brain, using Allen CCFv3 anatomical labels, at postnatal days (P) 4, 6, 8, 10, 12, and 14, and determine the volumetric growth of different brain regions. We utilize 11 different cell type-specific transgenic animals to validate and refine anatomical labels. Moreover, we reveal region-specific density changes in γ-aminobutyric acid-producing (GABAergic), cortical layer-specific cell types, and microglia as key players in shaping early postnatal brain development. We find contrasting changes in GABAergic neuronal densities between cortical and striatal areas, stabilizing at P12. Moreover, somatostatin-expressing cortical interneurons undergo regionally distinct density reductions, while vasoactive intestinal peptide-expressing interneurons show no significant changes. Remarkably, microglia transition from high density in white matter tracks to gray matter at P10, and show selective density increases in sensory processing areas that correlate with the emergence of individual sensory modalities. Lastly, we create an open-access web-visualization (https://kimlab.io/brain-map/epDevAtlas) for cell-type growth charts and developmental atlases for all postnatal time points.

DeMBA: a developmental atlas for navigating the mouse brain in space and time

“…We resampled them to isotropic 20 × 20 × 20 µm voxel size using AMIRA (version 6.3.0; https://www.thermofisher.com/no/en/home/electron-microscopy/products/software-em-3dvis/amira-software.html). We also used the P4 volume shared by Liwang and colleagues 5 , which was provided as a .tif file with isotropic 20 × 20 × 20 µm voxel size. All volumes were converted to .nii.gz files for further processing.…”

“…Efforts to construct such frameworks have almost exclusively focused on the adult brain, and atlases representing developing brain anatomy have consequently lagged behind. While some studies have addressed this by providing atlases for a subset of discrete, critical developmental stages [3][4][5] , this approach has notable limitations. First, when the temporal dimension is reduced to a subset of stages, data falling between established stages are not represented.…”

“…template (CCFv3 1 ; RRID:SCR_020999; postnatal day 56) to developing mouse brain templates (postnatal day 4, 7, 14, 21 and 28) sourced from multiple publicly shared datasets 5,8 . The transformations were based on a three-step (translation, affine, b-spline) registration using elastix 9 , optimised by manually defined regions and landmarks.…”