Mouse brain map
This image shows a cross-section from the “average” brain that serves as the basis for the Allen Institute’s 3-D mouse cortex map. A single neuron has been mapped onto the cortex in purple at upper left. (Credit: Allen Institute for Brain Science)

After years of painstaking work, Seattle’s Allen Institute for Brain Science has completed a digital 3-D map of the mouse cortex, filled out with annotations that trace the brain’s neurons, genetic correlations and the connections between different functional regions.

The project provides a standardized coordinate system that should help neuroscientists place data points like pins dropped on an online map, but in three dimensions.

“Maps of the brain have always been created in two dimensions, but even a stack of flat maps sitting on top of each other does not necessarily align with the complex three-dimensional nature of the brain,” Christof Koch, the Allen Institute’s president and chief scientific officer, said in a news release. “The Common Coordinate Framework is a remarkable effort to capture a typical mouse brain in its true three dimensions, and serves as a valuable platform on which to present many of our other data resources.”

To create the map, researchers analyzed the anatomical features of 1,675 specimens from the Allen Mouse Brain Connectivity Atlas. Over the course of three years, they smoothed out the gaps in the data and blended the two-dimensional imagery to produce an “average” mouse brain template.

Then they layered additional annotations – ranging from gene expression readings to functional imaging – onto the 3-D template. The researchers used genetic tracers to define the boundaries between 43 distinct regions of the cortex.

Lydia Ng, the institute’s senior director of technology, compared the task to creating the kind of guide map you can call up on your smartphone, complete with pointers to bus stops and restaurants.

“The ‘average brain’ is like the GPS components of the map,” she told GeekWire. “The annotation is like the Google Maps part of it. … The aspirational goal is to integrate all our data together.”

Ng said some anatomical features of the brain become clearer in when the readings from hundreds of brains are averaged out. For example, one brain region has barrel-shaped structures that are wired up to recognize sensations picked up by a mouse’s whiskers.

It’s difficult to make out the shapes of those barrels on an single photomicrograph, Ng said. “You get a much cleaner picture of those barrels [on the averaged-out brain] than you get from one experiment,” she said.

Brain template
Researchers used transgenic mouse lines and data from viral tracers to draw boundaries between 43 regions of the cortex. The end result is a template brain rendered faithfully in three dimensions. (Credit: Allen Institute for Brain Science)

Researchers already have started adding hundreds of reconstructed neurons from the institute’s Cell Types Database to flesh out the map further.

The Common Coordinate Framework is part of the institute’s October data release, which also includes several other updates to resources.

The Allen Brain Observatory, which was launched in May, received a back-end overhaul that enables robust search and the addition of more than 30 new data sets and additional engineered mouse lines. The Allen Cell Types Database and the Allen Mouse Brain Connectivity Atlas are have been updated with additional data.

Since its launch in 2003, the Allen Institute for Brain Science has received $500 million in financial support from Microsoft co-founder Paul Allen. And neuroscience isn’t the only scientific field backed by the billionaire: The Allen Institute for Artificial Intelligence, the Allen Institute for Cell Science and the Paul G. Allen Frontiers Group are also part of his research portfolio.

All of the Allen Brain Institute’s data and tools are publicly available online.

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