And the location of this complexity is surprising. Neuroscience has focused much of its research on the outer covering of the brain, responsible for memory, learning, language, etc. But the majority of cellular diversity is actually found in evolutionarily older structures deep within the brain, Lein explains.
How did they make these atlases?
The classic neuroscience approach to classifying cell types relies either on the shape of the cells (think star-shaped astrocytes) or the type of activity of the cells, such as fast-spiking interneurons. “These cell atlases capitalize on a new suite of technologies from genomics,” says Lein, primarily a technique known as single-cell sequencing.
First, researchers start with a small piece of frozen brain tissue from a biobank. “You take a tissue, you crush it, you profile lots of cells to try to make sense of it,” Lein says. They make sense of it by sequencing cell nuclei to examine the genes expressed. “Each cell type has a consistent set of genes that it typically uses. And you can measure all of these genes and then group all the cell types based on their overall gene expression pattern,” Lein explains. Then, using imaging data from the donor brain, they can place this functional information in its spatial place.
How can scientists use these brain cell atlases?
So many ways. But one crucial use is to help understand the causes of brain diseases. A reference atlas of the human brain depicting a normal or neurotypical brain could help researchers understand depression, schizophrenia, or many other types of illnesses, Lein says. Take the example of Alzheimer’s disease. You could apply these same methods to characterize the brains of people with different levels of Alzheimer’s disease severity, and then compare these brain maps with the reference atlas. “And now you can start asking questions like, ‘Are certain cell types vulnerable to disease, or are certain cell types responsible,'” Lein says. (He is part of a team already working on this topic.) Rather than studying plaques and tangles, researchers can ask questions about “very specific types of neurons that are the actual elements of the circuit that are likely to “be disrupted and have functional consequences,” he says. said.
What is the next step ?
Better resolution. “The next phase is really to cover the adult human and non-human primate brain and their development in a very comprehensive way.” In fact, this work has already begun with the BRAIN Initiative Cell Atlas network, a five-year, $500 million project. The goal is to generate a comprehensive reference atlas of human brain cell types across the lifespan, but also to map the cellular interactions that underlie a wide range of brain disorders.