A New Map of the Human Brain Contains 3,000 Previously Unknown Cell Types – Here Is What It Changes.

Researchers spent months cataloguing the genetic identities of individual cells extracted from donated human brains, one nucleus at a time, across more than a hundred different regions of the organ in a lab at the Allen Institute for Brain Science in Seattle. This task sounds almost unbearably tedious. Three adults who had consented to donate their brains to science before they passed away provided the tissue.

The result of that process, along with concurrent research at the Karolinska Institutet in Stockholm, was something that neuroscience had been striving for for decades but had not quite reached. A map. An actual cellular census of the human brain, published in 21 research papers concurrently in three major scientific journals in October 2023, rather than a schematic or rough model.

3,000 is the number that keeps coming up in this work’s coverage. The researchers found over 3,000 different types of brain cells, of which about 80% were classified as neurons and the remainder as different types of glial cells. Prior research had identified more than 100 cell types in particular areas of the cortex, the brain’s outermost and most researched layer. By extending that effort to nearly 100 regions throughout the entire organ, the new atlas discovered a tenfold multiplication of known complexity rather than a slight increase. No one had previously examined this level of resolution for many of those areas. They did not anticipate what they saw.

For the researchers who spent the most time analyzing the data, the most unexpected discovery had nothing to do with the cortex. The brain’s brainstem, which connects the cerebral hemispheres to the spinal cord and controls vital processes like breathing and heartbeat, is among the oldest structures in terms of evolution. It was found to contain the widest variety of neuron types in the entire organ. Some of these cells probably regulate innate behaviors, such as pain reflexes, fear, aggression, and sexuality, according to Professor Sten Linnarsson of Karolinska, whose group oversaw one of the two concurrent projects. The brainstem had been dismissed as the brain’s primitive region. It is now much more difficult to defend that assumption.

One category of the recently cataloged cells already has a colloquial name that conveys how unexpected it was to find it. The Allen Institute’s researchers refer to them as “splatter neurons.” According to Ed Lein, the senior investigator who has been a key figure in this work, when a three-dimensional cell of this kind is flattened into two dimensions for analysis—as they are frequently visualized—the outcome resembles a Rorschach test. Or, less kindly, similar to what occurs when a bug strikes a windshield while moving quickly. These cells are extremely intricate. It’s still unclear exactly what they do. In the context of a historic publication, that admission from one of the top brain researchers in the world is both candid and subtly startling.

The Human Genome Project has been compared to the atlas, and this comparison merits careful consideration. The stated objective of the genome project, which began in 1990, was to sequence the entire human DNA code. Despite the resources of an international consortium, this task was deemed unachievable by many and took thirteen years to complete.

Instead of producing a final product, it created a framework that served as a starting point for decades of research into illness, heredity, and the molecular causes of nearly everything that goes wrong in the human body. “We have now begun that journey,” Lein told BBC Science Focus, characterizing the atlas as the beginning of something similar. It’s a reasonable timeline, but it’s also important to keep in mind that decades later, the full practical benefits of the genome project are still being realized.

Researchers are already talking about specific enough medical implications to warrant serious consideration. For the first time, the atlas provides a comprehensive picture of the cell types found in a healthy brain. This makes it possible to compare that picture to brains affected by schizophrenia, Alzheimer’s, depression, autism, and epilepsy and ask with actual precision which cells are being disrupted, lost, or changed. Similar techniques have already been used by Linnarsson’s team at Karolinska to study glioblastoma, one of the most deadly brain cancers.

They found that the tumor cells behave like immature, disorganized stem cells that are attempting but failing to form a cohesive structure. This finding raises the possibility that the particular genes that are active in those cancer cells could eventually be used as therapeutic targets. It might not result in anything in the near future. However, there is now a framework for posing the question that did not previously exist.

Sitting with this research, there’s a sense that the brain is revealing itself to be more bizarre and complex than even the researchers had anticipated. It turned out that the most complicated parts were the oldest. The cells appear to be abstract art that no one could classify. Despite all of its details, the map is still only a first draft, according to its own authors. More cell types are anticipated by researchers. They don’t know how many. The next generation of neuroscientists will have to work in the gap between what they have created—a foundation that is both genuinely important and genuinely incomplete.