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Originally published Saturday, April 26, 2014 at 6:08 AM

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Milestones are reached in brain-mapping research

Two projects — both of them involving researchers from the Seattle-based Allen Institute for Brain Science — are reporting progress in mapping the brain, both the mouse brain and human fetal brains.


The New York Times

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As the Brain Initiative announced by President Obama a year ago continues to set priorities and gear up for what researchers hope will be a decadelong program to understand how the brain works, two projects independent of that effort reached milestones in their brain-mapping work.

Both projects, one public and one private, are examples of the widespread effort in neuroscience to create databases and maps of brain structure and function that can serve as a foundation for research. While the Obama initiative is concentrating on the development of new tools, that research will build on and use the data being acquired in projects like these.

One group of 80 researchers, working as part of a consortium of institutions funded by the National Institute of Mental Health, reported that it had mapped the genetic activity of the human fetal brain. Among other initial findings, the map, the first installment of an atlas of the developing human brain called BrainSpan, confirmed the significance of areas thought to be important in the development of autism.

In the second project, a group of 33 researchers, all but one at the Allen Institute for Brain Science, announced an atlas of the mouse brain showing the connections among 295 different regions.

Ed Lein, an investigator at Allen, was the senior author on the fetal brain paper. He said the research required making sections only 20 microns thick, up to 3,500 for each of four brains, two from fetuses at 15 weeks of development and two from about 21 weeks. The researchers measured the activity of 20,000 genes in 300 different brain structures.

One interesting finding, Lein said, was that “95 percent of the genome was used,” meaning almost all of the genes were active during brain development, significantly more than in adult brains. The team also found many differences from the mouse brain, underscoring the findings that, despite the many similarities in all mammalian brains, only so much can be extrapolated to humans from other animals.

The researchers also looked at genes that showed some association with autism in broad genome studies, and found that many of these genes were active during the formation of a part of the brain called the neocortex, which is important for functions like conscious thought. That supports the idea that the characteristic problems of autism have their origin in early development.

The brains came from the Birth Defects Research Laboratory at the University of Washington and Advanced Bioscience Resources Inc. in Alameda, Calif., and all federal ethics guidelines for the use of human tissue were followed.

Hongkui Zeng was the primary author on the mouse paper, which described the completion of a “connectome” of the whole mouse brain, meaning a map of connections. There are, of course, many connectomes that can be mapped — between large brain regions, for example, or down to the level of the connections between each brain cell and its neighbors.

Zeng reported the completion of a “mesoscale” connectome, meaning it was in the middle, tracing the connections among 295 brain regions deemed important to map. The result is the Allen Mouse Brain Connectivity Atlas, and like the BrainSpan data and other atlases completed at the Allen Institute, it is all publicly available.

The atlas, like others that Allen has produced, is meant as a foundation for research, but Zeng said interesting patterns have already emerged. The researchers’ method, injecting tracers into brain regions and using light microscopy to track the connections, showed not only the direction of information flow, but also the intensity of the connections between regions.

The strength of the connections varied so much that some were 1 million times stronger than others, she said, with a small number of very strong connections and a “sea of weak connections.”

The role of these widely distributed weak connections, Zeng said, is not known. She said they could be involved in modulating brain activity, or perhaps in memory.



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