Brain ‘census’ identifies 3,000 types of cells – 10/23/2023 – Science

An international team of scientists has mapped the human brain with unprecedented resolution. The brain atlas, a $375 million effort begun in 2017, has identified more than 3,300 brain cell types, an order of magnitude greater than previously reported. Researchers have only a vague idea of ​​what the newly discovered cells do.

The results were described in 21 articles published last week in Science and several other scientific journals.

Ed Lein, a neuroscientist at the Allen Institute for Brain Science in Seattle who led five of the studies, said the findings were made possible by new technologies that allowed researchers to examine millions of human brain cells collected from biopsied tissue or cadavers.

“It really shows what can be done now,” he said. “Opens a new era in human neuroscience.”

Still, Lein said the atlas is just an early draft. He and his colleagues have examined only a small fraction of the roughly 170 billion cells that make up the human brain, and future research will certainly discover more cell types.

The first time biologists realized that the brain was made up of different cell types was in the 1800s. In the 1830s, Czech scientist Jan Purkinje discovered that some brain cells had incredibly dense branches. Purkinje cells, as they are now known, are essential for fine-tuning our muscle movements.

Later generations developed techniques to make other types of cells visible under a microscope. In the retina, for example, researchers have found “cone cells” that capture light. By the early 2000s, researchers had found more than 60 types of neurons in the retina alone. They then wondered how many types of cells were hidden in the deeper regions of the brain, which are much more difficult to study.

With funding from the NIH (National Institutes of Health), Lein and his colleagues began mapping the brain by examining how brain cells activate different genes. At least 16,000 genes are active in the brain, and they are stimulated in different combinations in different cell types.

The researchers collected brain tissue from a variety of sources, including people who had recently died and those who were undergoing brain surgery.

When studying fresh brain tissue, scientists attached electrodes to the surface of individual cells to listen to their electrical activity, injected dye to observe their structure, and finally removed the cells’ nuclei to examine them more closely.

Instead of carrying out these procedures manually, researchers designed robots to work efficiently with the samples. The robots have already examined more than 10 million human brain cells, Lein estimated.

Some of the newly identified cells were found in layers of the cerebral cortex on the outer surface of the brain. This region is essential for complex mental tasks, such as using language and making plans for the future.

But new studies reveal that much of brain diversity lies outside the cerebral cortex. A large number of the cell types discovered in the project are in deeper regions of the brain, such as the brain stem leading to the spinal cord.

Researchers have found many new types of neurons, cells that use electrical and chemical signals to process information. But neurons make up only about half of the brain’s cells. The other half is much more mysterious.

Astrocytes, for example, appear to nourish neurons so they can continue to function properly. Microglia act as immune cells, attacking invaders and pruning some of the neurons’ branches to improve their signaling. And researchers have also found many new types of these cells.

Researchers have used some of the same methods to study the brains of chimpanzees and other animals. By comparing results across species, the researchers investigated how the human brain evolved to be different from those of other primates.

Previous studies suggested that the human brain could have distinguished itself thanks, in part, to the emergence of new cell types. But researchers were surprised to discover that every cell type in human brains matched those found in chimpanzees and gorillas, our closest living relatives.

Within these cells, the researchers discovered a few hundred genes that became more or less active in humans than in apes. Many of these genes are close to genetic switches that turn genes on or off.

Trygve Bakken, a neuroscientist at the Allen Institute who worked on primate studies, and his colleagues discovered that several of the genes that distinguish humans are involved in building the connections between neurons, known as synapses.

“It’s really the connections — how these cells are communicating with each other — that make us different from chimpanzees,” Bakken said.

Megan Carey, a neuroscientist at the Champalimaud Center for the Unknown in Portugal who was not part of the brain atlas project, said the research provided an impressive amount of new data for researchers to use in future studies. “I think this is a tremendous success story,” she said.

However, she also warned that understanding how the human brain works will not be a matter of simply cataloging each part down to the smallest detail. Neuroscientists will also have to take a step back and look at the brain as a self-regulating system.

“There will be answers in this data set that will help us get closer to that,” Carey said. “We just don’t know what they are yet.”

Adam Hantman, a neuroscientist at the University of North Carolina who was not involved in the study, said the atlas could be of great help for some types of research, such as tracking brain development. But he questioned whether a catalog of cell types would elucidate complex behaviors.

“We want to know what the orchestra is doing,” he said. “We don’t really care what this one violinist is doing right now.”