New cross-species map links mouse and marmoset brain regions

Most neuroscience research still runs on mice, even though much of what applies to mice does not hold up in humans. Marmosets have emerged as a bridge between species. However, comparing the brains of mice and marmosets runs into a chicken-and-egg problem. Scientists need to know which part of one brain matches the respective region of the other, but almost every brain map draws those areas differently.

In a new study, Cold Spring Harbor Laboratory Professor Partha Mitra and colleagues built the first cross-species map to systematically link mouse and marmoset brain regions.

It's the kind of problem that nobody wants to address, because it's hard."

Partha Mitra, Professor, Cold Spring Harbor Laboratory

Comparing genomes across species is relatively straightforward. DNA aligns letter by letter. But brain circuits vary even within one species. Compounding the problem, research teams have built different brain atlases that divide the same mouse brain differently.

Mitra's team noticed that experts often argue over grouping small structures into larger ones. For instance, some atlases group several brain regions into a single subcortical structure called the amygdala. In other atlases, the amygdala superstructure does not exist, and the component regions are instead grouped into the cerebral cortex. Perhaps surprisingly, most atlases agree on the smallest identifiable chunks of the brain, called "leaf-level regions."

Mitra's team matched leaf-level regions between mice and marmosets first, then built the bigger picture from there. "Think of states and cities," Mitra says. "State boundaries may shift, but at the lowest level, people tend to agree about cities. New York City might be called New York in one atlas and New Amsterdam in another, but everyone at least agrees that a city exists here."

The team picked through more than 100 published studies, manually matching only the smallest reliably identified parcels. They found a direct, one-to-one match for 43% of mouse brain regions and 47% of marmoset regions. They also found that the cerebral cortex has been subdivided into far more specialized regions in marmosets than in mice.

The result isn't a final answer, but a shared reference point other labs can now build upon. "This was an intermediate stepping stone," Mitra says. "Having this kind of map is helpful for asking how different regions of the brain are connected and then comparing those connections."

Why go through all that trouble? Many drugs that work in mice fail in humans. As Mitra puts it, "We are not mice. We are not even large mice." Marmosets, however, are evolutionarily much closer to humans. So, a more accurate comparison of mice and marmosets could make for a more reliable journey from lab results to healthcare applications and patient outcomes.

In the meantime, it should also help us better understand who we are-both as a species and as different-minded individuals.