A veritable atlas of human and non-human primate brain cells is presented in a series of 21 studies published in the journals Science, Science Advances and Science Translational Medicine (New Window).
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Three-dimensional images of neurons reconstructed from living brain slices. The variety of colors and shapes represents the wide variety of neuron subtypes that make up the human brain.
Photo: KAROLINSKA INSTITUTE WITH THE ALLEN INSTITUTE FOR BRAIN SCIENCE
The work, which began in 2017, was carried out as part of the BRAIN (for Brain Research through Advancing Innovative Neurotechnologies) initiative, overseen by the National Institutes of Health (NIH) in the United States. The Canadian neuroscientist Jesse Gillis from the University of Toronto took part in this international initiative.
A complex organ
The brain is certainly the most complex organ in the body. We are talking about more than 170 billion neurons. It is often compared to the number of stars in the galaxy, which is quite impressive, says Professor Martin Parent from the CERVO research center at Laval University, who was not involved in the work.
This work has also made it possible to identify many new types of neurons, cells that use electrical signals and chemical substances to process information.
In addition to neurons, there are glial cells, twice as small but twice as numerous, which are essential for the functioning of the brain as they play a supporting role. The latter occupy a corresponding volume in the brain, and the present work has also identified new ones.
All of these neurons and cells are connected to each other in a very precise way and form very complex networks, notes Professor Parent.
The question we always ask ourselves is whether the human brain will one day be able to understand itself! It’s still a big challenge.
And the answer is beginning to emerge.
A first draft
New studies report thousands of different brain cell types throughout the brain. For many parts of the brain, this complexity and diversity has never been described before, researchers at the Allen Brain Institute who were involved in the work explain in a press release.
The atlas allows the characterization of 3,313 cell types in the human brain, sometimes revealing features that distinguish it from other primates.
This rough map of human brain cells helps describe their shapes, locations, electrical activity patterns and genetic properties. Its creation was made possible thanks to new technologies that make it possible to study millions of human brain cells taken from corpses or during biopsies.
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A researcher holds a piece of a human brain that was donated for research after a person’s death.
Photo: Associated Press / Allen Institute/Erik Dinnel
Professor Parent believes this type of initiative, carried out with human brains – rather than animals – is very important because of the many differences between species. However, working with the human organ still presents some challenges as there are major differences between individuals.
At CERVO we work with a brain bank donated by people after their death. This creates a still image, a photo, at the moment of death. […] And the brains of animals used in research are very different from those of humans in terms of cellular composition and brain organization.
By observing many brains, we can get an idea of a so-called “normal” organization. We can then see what happens in certain pathologies to be able to detect changes, adds the researcher.
Similar, but different
In general, people have the same brain structure, but genetic and environmental factors also influence brain development and function.
Each person’s organ reflects their unique journey and life experiences. A better understanding of how all cell types in a healthy brain behave and interact with each other will ultimately help neuroscientists better understand the cell types associated with the diseases that occur there and identify the corresponding cells in the model.
When we note certain generalities from one brain to another, such as the thickness of different cell layers or the types of neurons present in different regions, there are notable differences between brains that are visible to the naked eye, notes Professor Parent .
For example, the surface of the cerebral cortex is arranged differently from person to person.
When we focus on creating an overall picture of the normal, healthy brain, we still need to be careful because individual variability is always observed. For example, a simple magnetic resonance imaging scan reveals different workings in the healthy brain of one person to another. People use their brains differently to respond to the same problem, the professor notes.
The accumulation of reliable and precise data will certainly make it possible to create a “kind of map of the brain” accessible to all researchers and whose precision will improve over the years.
humans and primates
One of the studies makes it possible to characterize the organization of brain cells specific to Homo sapiens in relation to non-human primates, a term that denotes all species of the order Primates that do not belong to the genus Homo.
In particular, they show, for example, that chimpanzee neurons are more similar to those of gorillas than to those of humans, even though chimpanzees and humans share a more recent common ancestor.
One of the studies also found that all cell types found in the human brain are also found in chimpanzees and gorillas. However, other work done in the past suggests that the human organ has excelled in developing new cell types over the course of evolution.
However, the researchers discovered several hundred genes in these cells that were more or less active in humans than in other great apes.
It’s really the connections – the way these cells communicate with each other – that sets us apart from chimpanzees, explains Allen Brain Institute neuroscientist Trygve Bakken, who was involved in the primate studies, in a press release.
In addition, the Allen Brain Institute team discovered that a number of the genes that characterize humans are involved in the development of synapses that connect neurons.
An instruction manual
This atlas allows us to better understand the cellular components of the brain, their number, their location and the way they are connected to each other. This makes it possible to better explain the development of diseases such as Alzheimer’s and schizophrenia, but also to enable targeted treatments based on cells.
Understanding the human brain at such resolution will not only help scientists determine which cell types are most affected by certain mutations that cause neurological diseases, but it will also lead to a better understanding of our human species, the press notes of the BRAIN Initiative.