A cubic millimeter of human brain reveals a greater set of neuronal connections

57,000 cells, almost 150 million synapses and 230 millimeters of blood vessels. All of this fits in just one cubic millimeter of human brainwhich is equivalent to 1,400 terabytes of data and represents an unprecedented view of the structural organization of brain tissue.

Harvard University (USA) and Google Research collaborated for almost a decade to generate the largest 3D reconstruction with synaptic resolution of a piece of human temporal cortex approximately half the size of a grain of rice.

The nanoscale reconstruction, reported in a study published by Science, shows each cell and its network of neuronal connections in detail, giving an unprecedented view of the structural organization of brain tissue at the supracellular, cellular and subcellular levels.

The human brain is an enormously complex organ and to date little is known about its cellular microstructure, but it is known that alteration of synaptic and neuronal circuits influences numerous brain disorders.

The researchers, led by Jeff Lichtman of Harvard University and Viren Jain of Google Research’s Connectomics team, combined artificial intelligence and electron microscopy to color-code and reconstruct the wiring of that small piece of brain.

Knowing human neural circuits in such detail entails a series of challenges, such as technological limitations or the difficulty of having access to high-quality tissue. Biopsies are rare and are used to examine or remove neoplastic masses, which prevents investigation of the normal structure of the human brain.

The team used as a basis for the study a sample removed during a surgical procedure to access an underlying lesion of the hippocampus of a patient with epilepsy.

The researchers reconstructed “thousands of neurons, more than one hundred million synaptic connections and the rest of the tissues, including brain matter, glial cells, blood vasculature and myelin“, they explain in the study.

An unprecedented vision

This unprecedented view of a piece of the human brain allowed us to discover aspects of the temporal cortex that had never been seen before, such as the existence of a rare but powerful set of axons (part of the neuron that transmits brain signals) connected by up to 50 synapses.

Other details are the large number of glia cells (responsible for ensuring the survival of neurons) compared to neurons, in a ratio of two to one, or that oligodendrocytes (responsible for the formation of myelin) are the most common.

The team also developed a set of open-access tools that other researchers can use and hope that “other studies using this resource can provide valuable insights into the mysteries of the human brain,” the study indicates.

For its authors, this research demonstrates “the feasibility of human connectomic approaches to visualize and ultimately understand the physical underpinnings of normal and altered human brain functioning.”

Connectome, the diagram of neuronal connections

Connectomics, analogous to genomics, aims to create complete catalogs of brain structure, down to individual cells and wiring. Achieving complete maps would open the way to new insights into brain function and diseases, about which scientists still know very little.

The connectome is the diagram of neuronal connections and without it you cannot understand how the brain works. The first attempt to achieve a map of this type was made in the seventies with the roundworm, the result was partial.

The big step was taken last year, when the complete brain connectome of the larva of “Drosophila melanogaster” (vinegar or fruit fly), after twelve years of work.

Now, Harvard University and Google are also involved in the BRAIN Initiative, a project to map in high resolution the neuronal wiring of an entire mouse brain, which will begin with the formation of the hippocampus, important for neuroscience for its role in memory and neurological diseases.

The result would be about 1,000 times the amount of data they just produced from the one-cubic-millimeter fragment of human cortex.

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