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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 to date, published 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 this new study, 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.
"It is by far the most comprehensive and thorough analysis of all cortex regions in all species. We can now say that we understand the distribution rules of the parts list, "said Hongkui Zeng, executive 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 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 to reach cell types, and that's really the fundamental goal of the Allen Institute," said Janelia's Karel Svoboda, who led the neuron study. engines with Michael Economo. author on the study of 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 measurements of neuronal 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 organizational rules identified in this study to be applied in the whole 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.
"Only thanks to recent technological advances can we measure the activity of so many genes in a single cell," said Bosiljka Tasic, associate director of molecular genetics at the Allen Institute and the first publication on the study of cell types. "At the end of the day, we are also working to study not only gene expression, but also most other cell properties, including their function, which is the most difficult to define."
The Allen Institute-led cell-type study was designed from a similar smaller study conducted in 2016 that examined approximately 1,600 cells in the brain portion dedicated to visual mouse processing. 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 whole picture."
SOURCE: Allen Institute for Brain Science
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