3D mouse brain atlas provides a more dynamic 360-degree picture of development

A 3D atlas of the developing mouse brain using advanced imaging and microscopy techniques has been created by a team of researchers from the Penn State College of Medicine and collaborators from five different institutes. This new atlas provides a more dynamic 360-degree picture of the entire mammalian brain as it develops during the embryonic and immediate postnatal stages and serves as a common reference and anatomical framework that will help researchers understand the brain development and to study neurodevelopmental disorders.

They published their work today October 21 in Natural communications.

“Maps are fundamental infrastructure on which to build knowledge, but we don’t have a high-resolution 3D atlas of the developing brain,” said Yongsoo Kim, associate professor of neural and behavioral sciences at Penn State College of Medicine and lead author of the study. paper. “We generate high-resolution maps that we can use to understand how the brain develops under normal circumstances and what happens when a brain disorder appears.”

Geographic atlases are a set of maps that provide a comprehensive view of Earth’s geography, including boundaries between regions and countries, features such as mountains and rivers, and transportation routes like roads and highways. Importantly, they provide a common understanding that allows users to identify specific locations and understand the spatial relationships between regions.

Likewise, brain atlases are fundamental to understanding the architecture of the brain. They help researchers visualize how the brain is spatially organized and understand the structure, function, and how different regions and neurons are connected. Previously, scientists were limited to 2D histology-based snapshots, making it difficult to interpret anatomical regions in three dimensions and any changes that might occur, Kim said.

In recent years, enormous advances have been made in whole-brain imaging techniques, which allow researchers to observe the entire brain at high resolution and produce large-scale 3D datasets. To analyze this data, Kim explained, scientists developed 3D reference atlases of the adult mouse brain, which is a model for the mammalian brain.

Atlases provide a universal anatomical framework that allows researchers to overlay diverse data sets and conduct comparative analyses. However, there is no equivalent for the developing mouse brain, which undergoes rapid changes in shape and volume during embryonic and postnatal stages.

“Without this 3D map of the developing brain, we cannot integrate data from emerging 3D studies into a standard spatial framework or analyze the data coherently,” Kim said. In other words, the lack of a 3D map hinders the advancement of neuroscience research.

The research team created a common multimodal 3D coordinate frame of the mouse brain across seven developmental time points: four time points during the embryonic period and three time periods during the immediate postnatal phase.

Using MRI, they captured images of the overall shape and structure of the brain. They then used light-sheet fluorescence microscopy, an imaging technique that allows the entire brain to be viewed at single-cell resolution. These high-resolution images were then fit to the shape of the brain MRI models to create the 3D map. The team pooled samples from male and female mice.

To demonstrate how the atlas can be used to analyze different datasets and track how individual cell types emerge in the developing brain, the team focused on GABAergic neurons, which are nerve cells that play a key communication role in the brain. This cell type has been implicated in schizophrenia, autism and other neurological disorders.

Although scientists have studied GABAergic neurons in the outermost region of the brain called the cortex, little is known about how these cells appear throughout the brain during development, according to the researchers. Understanding how these groups of cells develop under normal conditions can be key to assessing what happens when something goes wrong.

To facilitate collaboration and advancements in neuroscience research, the team created an interactive web version that is publicly accessible and free. The aim is to significantly reduce the technical barriers that prevent researchers around the world from accessing this resource.

“This provides a roadmap that can integrate many different data (genomics, neuroimaging, microscopy, etc.) into the same data infrastructure. This will drive the next evolution of brain research, driven by machine learning and artificial intelligence,” Kim said.