An Atlas of the Human Brain

Brain

The diversity of brain cells and their genetic activity is now recorded in a new brain atlas.© fruttipics/ iStock

As part of a large-scale international research project, researchers have mapped the human brain at the cellular level. They characterized more than 3,000 different cell types and uncovered features that distinguish us from other primates. The results also show large individual differences between the brains of different people and provide insights into the molecular basis of neurological diseases. From the perspective of those responsible, the studies now published mark the starting point of a new era in brain research.

Our brain consists of trillions of nerve cells that are interconnected in a complex network. Since 2017, researchers worldwide have been working under the leadership of the American National Institutes of Health in the BRAIN Initiative Cell Census Network (BICCN) to understand the architecture of this network in more detail. The aim is, among other things, to gain insights into normal functioning and pathological changes, to draw comparisons to other species and to understand the development of the brain from embryo to adult.

New insights thanks to innovative techniques

In 21 studies published in the journals Science, Science Advances and Science Translational Medicine, the research consortium is now presenting the results of the project - including a detailed atlas of the cells of the human brain. To characterize the cells and their genetic makeup, the research teams involved used a variety of methods, some of which have now been applied to human cells for the first time. “Traditionally, the techniques have been used primarily in preclinical studies with rodents and other experimental models,” explains Science editor Mattia Maroso. “The work presented here shows how research on humans could now catch up with preclinical work.”

The basis was the brains of three adult men who made their brains available for research after their deaths. In addition, the researchers used tissue donations from living people whose brain tissue was removed during brain operations - for example because of severe epilepsy or tumors. They analyzed the so-called methylation pattern of DNA for more than half a million brain cells, which determines which parts of the genome are converted into proteins in each cell through deposits in the genetic material. In addition, they recorded the three-dimensional structure of the DNA as well as the proteins and the entirety of the protein blueprints in the cells that were read and copied into RNA.

In health and illness

The researchers identified more than 3,000 different types of brain cells. Around 80 percent of them are nerve cells, the rest are different types of glial cells that support, supply and electrically insulate the nerve cells. Using deep learning models, a research team led by Yang Li from the University of California, San Diego, uncovered connections between the frequency of certain brain cell types and neuropsychiatric disorders, including schizophrenia, bipolar disorder, Alzheimer's disease and major depression. In the future, these findings could help to better assess the individual risk of these diseases and possibly take early measures for prevention and treatment.

Another study led by Nelson Johansen of the Allen Institute for Brain Science in Seattle found that although the basic cellular architecture of the brain is the same in different people, there are large individual differences in the extent to which which cells are represented and how active they are. Gene expression is therefore influenced by, among other things, a person's age, gender, ethnicity and health status, although many other potential influencing factors are still unclear. “There is no single prototypical human,” write Alyssa Weninger of the University of North Carolina at Chapel Hill and Paola Arlotta of Harvard University in Cambridge in an accompanying commentary, also published in the journal Science. “There is a spectrum of differences in genetic variation and response to the environment in both healthy individuals and disease.”

Uniquely human

Despite individual differences in gene expression, there are some fundamental characteristics that make us unique as humans. This is shown by a study led by Nikolas Jorstad from the Allen Institute for Brain Science in Seattle based on comparisons with the brains of non-human primates such as chimpanzees and gorillas. Although chimpanzees are evolutionarily more closely related to humans than to gorillas, their neurons are more similar to those of gorillas. Although the basic cell types are the same, other genes are active in human neurons that are important, among other things, for the networking of nerve cells. "This is a plausible explanation for how cognitive abilities have increased over the course of evolution, namely by rewiring circuits from the same cell types or by changing the performance of the system in slightly different ways," says Jorstad's colleague Ed Lein.

The brain atlas data is now freely available to scientists around the world. “The data collected by BICCN will now enable researchers to address fundamental scientific questions about the human brain,” writes Maroso. “The era of cellular research on the human brain is just around the corner.”

Sources:
Mattia Maroso (American Association for the Advancement of Science), Science, doi: 10.1126/science.adl0913; Yang Li (University of California, San Diego) et al., Science, doi: 10.1126/science.adf7044; Nikolas Jorstad (Allen Institute for Brain Science, Seattle) et al., Science, doi: 10.1126/science.ade9516

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