Down the avenues and alleyways (Image: Allen Institute for Brain Science)

IT’S not quite as simple as X marks the spot, but uncovering the roots of neural disorders should be much easier now that we have a complete brain map.

The Allen Mouse Brain Connectivity Atlas is the first detailed map of any mammal’s neural network. With the equivalent for the human brain still years away, it’s an essential stepping stone and should provide insights into conditions such as schizophrenia.

“This is a huge leap for modern neuroscience,” says Martijn van den Heuvel at the University Medical Center in Utrecht, the Netherlands. “It will be a reference data set for years of computational neuroscience to come.”


This is a huge leap for modern neuroscience. The mouse connectome will be a model for years to come

The work complements the BRAIN Initiative that Barack Obama’s government announced almost a year ago. Among other things, the decade-long mission aims to develop new technologies for studying the electrical activity of the brain in action. But before we can look at its traffic flow, we need a basic route map of the interconnections, known as a connectome. To date, we only have a complete connectome down to the level of individual neurons for the simple nematode worm. Connectomes have been drawn up for other animals, including humans, but they are much cruder. They show connections between brain regions rather than brain cells.

The mouse connectome lies somewhere in between. Rather than mapping every neuron, it traces connections between tiny cubes of brain tissue containing between 100 and 500 neurons.

Hongkui Zeng and colleagues at the Allen Institute for Brain Science in Seattle, Washington, injected the brains of 469 mice with a virus that introduced a fluorescent protein into the neural network. “The protein travels by diffusion through the cells like electrical signals travel through the brain,” Zeng says.

Because each animal was injected at a slightly different location, when taken together, the fluorescing proteins gave a snapshot of the network’s shape. Next, the team diced up each brain into 500,000 pieces each measuring 100 micrometres cubed. Based on the strength of fluorescence in the cubes, they generated a 3D map of how each of the 469 different signals spread through the brain’s thoroughfares and quieter byroads. The result is the most detailed map yet of the mouse brain’s entire neural network (Nature, DOI: 10.1038/nature13186).

Neuroscientists think that conditions such as schizophrenia and autism stem from problems in neural connectivity. “Virtually all major clinical brain disorders are associated with disturbances of brain connectivity,” says Olaf Sporns at Indiana University in Bloomington. Crude maps, like the one of the human brain, show the broad patterns of neural connectivity. They give some clues about why these diseases occur, but more detailed maps, such as this, will pinpoint where the problems lie – providing precise targets for therapies.

We have mouse models for many of these diseases, says Zeng, so we can treat the brains of affected animals with the same dye-and-dice approach. It should then be possible to produce an “autism connectome”, say, that can be compared with the healthy connectome just published. “It sets the stage for us to look at disease conditions,” she says.

The time brain problems begin A detailed neural map of the mammalian brain will help us to work out what triggers conditions like autism (see main story) – but it can’t tell us when the problems begin. A new atlas of the developing human brain should offer clues. Ed Lein at the Allen Institute for Brain Science in Seattle, Washington, and colleagues looked at the brains of four human fetuses between 15 and 21 weeks old. Using a microscope with a laser attached, they precisely cut the brains into slices 20 micrometres thick and stained them to identify the different brain structures. The team then analysed the structures to work out which genes were active. The result is called the BrainSpan Atlas of the Developing Human Brain (Nature, DOI: 10.1038/nature13185). By this stage in fetal development, most of the brain’s regions and structures are in place, says Lein. His team is now looking at patterns of gene activity in the four brains to work out whether it is possible to detect early signs associated with conditions like autism. This should help narrow down when and where such conditions begin in the developing human brain. What’s more, because of the precision afforded by the laser dissection, it should be possible to identify the precise groups of cells implicated rather than simply identifying the brain region involved. The team has already found that a collection of genes associated with autism is particularly active in the newly developed excitatory neurons in the cortex. That will give researchers a target should they wish to develop a prenatal diagnostic tool for autism, says Lein.

This article appeared in print under the headline “Brain map to zoom in on neural blips”