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Scientists Unveil First Wiring Diagram for Mouse Brains

A detailed map showing the connections inside a mammalian brain has been revealed, achieving a key milestone for the $100 million BRAIN Initiative.
Image: Mouse connections
This computerized image shows connections between four distinct visual areas in the mouse cortex, in green, yellow, red, orange. These cortical areas are highly interconnected with each other and with additional areas involved in vision in the thalamus, shown in pink, and the midbrain, shown in purple.Allen Institute via AP
/ Source: Reuters

WASHINGTON — A year to the day after President Barack Obama announced a $100 million "BRAIN Initiative" to accelerate discoveries about how gray matter thinks, feels, remembers and sometimes succumbs to devastating diseases, scientists on Wednesday said they had achieved a key milestone toward that goal.

Writing in the journal Nature, they unveiled the mouse "connectome," a map showing the sinuous connections that neurons make throughout the mouse brain as they form functional circuits.

The mouse connectome "provides the most detailed analysis of brain circuitry currently available for any mammalian brain," said neuroscientist David Van Essen of Washington University in St. Louis. "It is truly a landmark study."

Van Essen is a co-leader of the human connectome project, which aims to do the same sort of analysis for Homo sapiens.

What is a connectome?

A connectome is essentially a wiring diagram. It shows how each of the millions or billions of neurons (gray matter) in a brain each connect to thousands of other neurons through projections called axons, the white matter, and thereby allow brain regions to communicate to produce behavior, intelligence and personality.

Such a diagram could reveal, say, how neurons that register the taste of a cookie fan out to circuits that store memories and unleash a torrent of remembrances of things past. And it could reveal what causes those circuits to malfunction in diseases such as Alzheimer's.

Image: Mouse connections
This image shows a top-down view of connections originating in different cortical areas of the mouse brain.Allen Institute via AP

Before the mouse, the only species for which scientists had created an essentially complete connectome was the roundworm C. elegans. It has 302 neurons.

The human brain has some 86 billion, each making as many as 10,000 connections.

Making neurons shine

For the mouse connectome, scientists led by Hongkui Zeng of the Allen Institute for Brain Science in Seattle used some of the 21st-century techniques that are required to create a human connectome. For the mouse, the key was to make neuronal connections literally shine.

To do that, Zeng's team injected viruses into precise spots in the brains of living mice. The viruses produce a special protein that fluoresces green. When the glowing protein diffuses throughout the neurons and their axons, the circuits show up under a microscope after the mouse is killed and its brain is sliced into sections.

Out of 295 distinct structures in the mouse brain, the technique revealed the neuronal highways into and out of all but 18. Many of the missing ones are tiny structures close to the bottom of the brain that were hard to hit with the virus.

Image: Wiring diagram
This image shows a circular wiring diagram of connections among 215 distinct regions throughout the mouse brain. Connections originating from 11 cortical regions are highlighted in different shades of colors, with the rest shown in gray.Allen Institute via AP

The map revealed several surprises about brain wiring. Connections that stay on one side of the brain "seem to be always stronger" than those that cross hemispheres, Zeng said.

The mouse's neuronal connections also vary widely in strength. That "must be contributing to brain network computation," she said. "We think a small number of strong connections and a large number of weak connections may be a fundamental network organization property to allow greater capacity of information processing."

The future of the brain

The mouse connectome unveiled on Wednesday is a medium-scale map, showing long-range and local connections. It does not have the resolution to reveal the precise neuron-to-neuron connections, or synapses, as a "microscale" connectome would, though that is a goal.

A large-scale map is the goal of the Human Connectome Project, which the National Institutes of Health announced in 2010 and which Van Essen calls "one of the great scientific challenges of the 21st century." It is being produced using special technique called diffusion tensor imaging in living brains.

The human connectome will resemble the Human Genome Project in a key way. Just as the genome project discovered the precise sequence of three billion molecules common to the vast majority of humans' DNA, serving as a reference book against which to measure individual genetic differences, so the connectome will first reveal neuro-commonalities and, eventually, the uniqueness of each individual brain.

— Sharon Begley, Reuters