The brain is our most complex organ, and little is known about its smallest building blocks. Scientists from the top American university Harvard and Google have now lifted the veil by mapping a cubic millimeter of cerebral cortex in unprecedented detail. The reconstruction contains approximately 57 thousand cells, 230 millimeters of blood vessels and almost 150 million synapses, the connections between two nerve cells.
That cubic millimeter – the size of a grain of salt – first saw the light of day not in the morgue, but in the operating room. An epileptic focus was removed from the woman to whom the piece of brain belonged. To access this, the surgeon first had to remove a piece of unaffected cerebral cortex.
A unique opportunity for scientists to admire a healthy, living piece of the brain. Even before the cell breakdown started, it was under the microscope, the researchers write Science.
To this end, the researchers first immersed the piece of cerebral cortex in a cocktail of preservatives and metals. Depending on the type of structure – cell organelles, cell nucleus, cell wall – these metals deposit on the different cell parts. They then placed the cubic millimeter of cerebral cortex under the microscope.
And not just any microscope: instead of light, this microscope fires electrons. These are transmitted to a greater or lesser extent, depending on the amount of metal that has settled on each structure. Just like with a light microscope, this produces a contrast between different structures, but the shorter wavelength of electrons makes many more details visible.
Detailed pictures
Scientists have been able to identify cell parts with this technique for some time now. Previously, this resulted in a number of detailed images – now computers stick thousands of such images together, creating a three-dimensional reconstruction.
Compare it with the immersive viewfeature in Google Maps: instead of a front view of buildings on the street, you now float 360 degrees around them. This makes the shape of brain cells, which consist of a cell body and branches arising from it, and the way in which those branches are connected to each other, fully visible.
“The combination of advanced computer analyzes and the exceptionally fresh tissue makes these data very valuable,” says Paul Lucassen, professor of brain plasticity at the University of Amsterdam, who was not involved in the research. ‘This has never been shown in such detail before.’
The researchers make a number of remarkable observations. For example, they see that one end of a brain cell sometimes connects to different ends of other brain cells, while until now it was always thought that one end connects to one other end. They also see an L-shaped cell, with one large extension upwards and one to the side, which they cannot properly identify. ‘That is quite unusual,’ says Lucassen. “Usually human brain cells extend upwards and downwards.”
It is not yet possible to say whether the researchers came across undiscovered, universal properties of the human brain. ‘Of course it is only one piece of cerebral cortex, from one person,’ says Lucassen. Moreover, it cannot be ruled out that it is affected by epilepsy or years of use of anti-seizure medication. ‘On the other hand, that makes it interesting for research into epilepsy.’
Extra valuable: the researchers make their dataset available to everyone. This allows other scientists to view the brain cells and compare the data with their own research.
