A "complete list" of the brain built from its components, cells

Neuroscientists at the Allen Institute have taken a step closer to understanding the complete list of cell types in the brain. In the most comprehensive study of its kind so far, published today on the cover of the newspaper Nature, the researchers sorted the cells of the cortex, the outermost shell and the cognitive center of the brain, into 133 different "cell types" according to the genes activated and deactivated by the cells.

The classification, based on 15 years of work at the Allen Institute, uncovered many rare brain cell types and laid the foundation for revealing the new functions of two of these rare neuron types. The study captured cell-by-cell information from parts of the mouse cortex involved in vision and movement.

Scientists are far from understanding how the mammalian brain does what it does. They do not even know what it's all about: the different types of brain cells. What neuroscientists face in their work is trying to recreate a delicious and complex meal, not only without knowing the ingredients and the recipe used to prepare it, but without even having the opportunity to describe many of these ingredients.

In the new study, the researchers found a way to describe these ingredients by analyzing the genes of nearly 24,000 of the 100 million mouse brain cells, creating a list of 133 cell types. Because the study captured the activity of tens of thousands of genes from so many cells and is almost complete for the visual and motor regions of the study, the other regions of the cortex will probably follow the same rules of organization, the researchers said.

"This is by far the most complete and thorough analysis of all the regions of a species' cortex. We can now say that we understand the rules of distribution of the list of its parts, "said Hongkui Zeng, Ph.D., chief executive officer. Director of Structured Science at the Allen Institute for Brain Science, a division of the Allen Institute, and lead author of the study. "With all this data in hand, we can begin to learn new principles about how the brain is organized – and ultimately, how it works."

In an accompanying document, also published today in Nature and led by researchers at the Janelia Research Campus of the Howard Hughes Medical Institute, neuroscientists have used gene classification and additional information on the shape of neurons to discover two new types of neurons involved in motion. The researchers then measured the activity of these different neurons in moving mice and discovered that one type is involved in movement planning, while the other type can trigger the movement itself.

"Gene expression is a very effective way of targeting cell types, and it's really the primary focus of the Allen Institute," said Karel Svoboda, Ph.D. of Janelia, who led the study on motor neurons with Michael Economo, Ph.D., and is also co-author of the study on cell types. "The study on the motor cortex is the first salvo in a different type of cell-type classification, where information on gene expression, structural information and measures of neural activity are gathered. to make statements about the function of specific cell types in the brain. "

Browse 24,000 cells to understand the brain

Mammalian cortex is considered to be the main brain region controlling cognitive function and is much larger in humans than in most other mammals. Many researchers believe that understanding the composition of this complex but regularly ordered brain region will help us understand what makes the mammalian brain special – or what makes our brains uniquely human. Researchers at the Allen Institute are also working on defining the "list of ingredients" for the rest of the mouse cortex, although they expect many of the rules to be met. Organization identified in this study be applied throughout the region. And the knowledge gained from the mouse cortex is the foundation for understanding the human cortex through comparative studies.

Although there are many ways to understand what differentiates a cell type from a cell type – its shape, how it sends electrical signals and how these signals translate into the many functions of the brain – only gene expression lends itself to the study of tens of thousands of cells. cell at a time, globally.

"It is only thanks to recent technological advances that we can measure the activity of so many genes in a single cell," said Bosiljka Tasic, Ph.D., associate director of molecular genetics at the University of California. Allen Institute for Brain Science and the first author of the study of cell types. "Ultimately, we are also working to study not only the expression of genes, but also many other cell properties, including their function, which is the most elusive, the most difficult to to define."

The cell type study conducted by the Allen Institute was built from a similar smaller study completed in 2016, which examined about 1,600 cells from the brain part of the visual processing of the mouse. By multiplying by 15 the number of cells analyzed and moving to a second region of the cerebral cortex, the researchers were able to create a more complete and detailed catalog of cell types.

"When we see not only the types of cells that people have identified before, but also a number of new cells that appear in the data, it's really exciting for us," Zeng said. "It's like we can put together all the pieces of the puzzle and suddenly see the picture as a whole."

Explore further:
The publication of the Allen Institute for Brain Science database almost doubles data on mouse brain cells

More information:
Shared and distinct types of transcriptomic cells across neocortical areas, Nature (2018). DOI: 10.1038 / s41586-018-0654-5, https://www.nature.com/articles/s41586-018-0654-5

Pathways of the descending motor cortex distinct and their roles in movement, Nature (2018). DOI: 10.1038 / s41586-018-0642-9, https://www.nature.com/articles/s41586-018-0642-9