Mammalian brains, with their unmatched number of nerve cells and density of communication between them, are the most complex networks known. While methods to analyze neuronal networks sparsely, accessing about one in every ten thousandth nerve cell have been available for decades, the dense mapping of neuronal circuits by imaging each and every synapse and all neuronal wires in a given piece of brain tissue has been a major challenge.

In an article published today in Science, researchers from the Max Planck Institute for Brain Research in Frankfurt, Germany, report that they succeeded in the dense connectomic mapping of about half a million cubic micrometers of brain tissue from the mouse cerebral cortex using 3-dimensional electron microscopy and AI-based image analysis.

Unlike any other organ, our brains contain extremely densely packed networks of membranous cables that are used by our about 86 billion nerve cells for communication amongst each other. Since each nerve cell in the main part of mammalian brains, the so-called cerebral cortex, communicates with about 1,000 other nerve cells via synapses placed along these cables over long distances, one expects a total of about 5 million kilometers of wires packed into our skulls – more than 10 times longer than all highways on our planet, in each of our brains.

The cables we find in our (and other mammalian) brains are as thin as 50 to 100 nanometers in diameter, about 1000th the diameter of our hairs. The resulting cable convolute is of such density and magnitude, that for more than 100 years, researchers have been able to only map connectivity between a miniscule fraction of neurons in a given piece of brain.

Only the development of faster electron microscopic techniques (“3D EM”) and of more efficient image analysis routines has made the dense mapping of neuronal networks possible. The novel field of “connectomics” has been pursuing the dense mapping of ever larger circuits in several species and brain regions.

In the work published in Science, a team around Max Planck Director Moritz Helmstaedter imaged and analyzed a piece of tissue from the cerebral cortex of a 4-week old mouse, obtained via biopsy from the somatosensory cortex, a part of the cortex occupied with the representation and processing of touch. Here, the researchers applied optimized AI-based image processing and efficient human-machine interaction to analyze all of the about 400,000 synapses and about 2.7 meters of neuronal cable in the volume.

With this, they produced a connectome between about 7,000 axons and about 3,700 postsynaptic neurites, yielding a connectome about 26 times larger than the one obtained from the mouse retina more than half a decade ago. Importantly, this reconstruction was at the same time larger and about 33-times more efficient than the one applied to the retina, setting a new benchmark for dense connectomic reconstruction in the mammalian brain.

Source: MPG