Mapping the Nervous System May Shed Light on the Origin of Different Neurological Diseases

The nervous system is composed of thousands of different neurons and immune cells, but information of cell types is limited to microscopy. Researchers recently developed a systematic map of the cell types that make up the mouse nervous system, which has the ability to reveal new information about the origin of neurological diseases, and may lead to a detailed map of the human brain.

The researchers at Karolinska Institute measured gene activity in individual cells in order to develop methods for mapping cell types of the brain systematically. Through this method, the researchers were able to identify 265 different types of cells and found that neurons had the greatest diversity with more than 200 different types.

“You can compare it to the difference between a medieval map and a satellite image: thousands of details that were previously invisible become visible with the use of these new techniques, and the entire map becomes more reliable,” Sten Linnarson, professor at the Department of Medical Biochemistry and Biophysics at Karolinska Institute, said in a statement.

This atlas of the mouse nervous system represents the first step in gaining knowledge of the cell types of the brain, which can be used to understand the origin of different diseases. Although past genetic studies have identified the genes that contribute to diseases, including schizophrenia and multiple sclerosis, the development of a new atlas of the nervous system will demonstrate the specific cells, their location, and time the relevant genes are active, the authors explained.

"With the help of our new atlas of the nervous system, researchers are now able to place disease-causing genes in specific cell types, which provides us with clues as to how the disease occurs,” Linnarson said. “In the long run this might contribute to the development of new drugs or other therapies."

The researchers conducted a comprehensive survey of the adolescent mouse nervous system by dissecting and analyzing 19 regions of the nervous system, including the peripheral sensory, enteric, and sympathetic nervous system. Using this data, the researchers used RNA sequencing of half a million single cells to create their detailed census of cell types.

“We discovered 7 distinct, regionally restricted astrocyte types that obeyed developmental boundaries and correlated with the spatial distribution of key glutamate and glycine neurotransmitters. In contrast, oligodendrocytes showed a loss of regional identity followed by a secondary diversification,” concluded the authors. “The resource presented here lays a solid foundation for understanding the molecular architecture of the mammalian nervous system and enables genetic manipulation of specific cell types.”

Reference

Zeisel A, Hochgerner H, Lönnerberg P, et al. Molecular architecture of the mouse nervous system. Cell. 2018;174(4):999-1014.E22. doi: 10.1016/j.cell.2018.06.021.