The most detailed cellular map of a mouse’s brain to date could deepen our understanding of how the organ evolved in mammals and what goes wrong in certain neurological conditions.
Various research groups have previously mapped hundreds of cell types across the mouse brain, but these were often based on a relatively small sample of cells.
To create a more detailed map, Hongkui Zeng at the Allen Institute for Brain Science in Seattle and her colleagues measured the activity of around 20,000 genes in 4.1 million cells from across the brains of hundreds of mice. These cells cover roughly 5 per cent of the total number estimated to exist in a mouse brain.
Based on gene activity, the researchers defined 5200 cell types. Of these, 5000 were neurons, which sends electrical impulses between different areas of the brain.
The remaining 200 cell types include astrocytes, which help to regulate blood flow in the brain, and oligodendrocytes, which produce the insulating layer myelin that helps neurons to transmit impulses.
Next, the team compared this gene activity data with that from cells in thin brain slices collected from one mouse. These slices hold information on where cell types are located, allowing the researchers to map how the cell types are spread across the brain.
They found that the upper part of the brain, which is involved in reasoning and self-control, contains a smaller range of neuron types, but these are relatively distinct from each other. The lower part of the brain, which maintains core bodily processes and regulates appetite, is made up of a greater number of different neuron types, yet these are more similar to each other.
This suggests that the lower part of the mouse brain has been more strongly conserved through evolution because maintaining bodily processes is more critical for an animal’s survival than regulating reasoning and self-control, says Zeng.
The resulting brain map, which provides information on around 10 times more cell types than previous maps, could provide new insights into how the human brain works and what goes wrong in some medical conditions, such as dementia.
“Cells are the functional units of the brain,” says Zeng. “This cell catalogue will help us pinpoint how circuits of cells contribute to behaviour, learning, emotion or disease. It could help us pinpoint vulnerable cells to target for treating diseases.”
However, because the map was constructed solely using mice from one inbred strain, further work will be needed to establish how these findings translate to other mice, as well as other mammalian species, including humans, says Zeng. Some cell types are also missing from the map due to only 5 per cent of the cells being sampled, she says.
“This work provides an essential list of cell type parts to build a brain,” says Yongsoo Kim at Pennsylvania State University. How these cell types differ or remain similar across various animal species will help advance our understanding of brain evolution among mammals, which could improve the translation of research carried out in animals to people, he says.
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