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Mammal’s tiny brain charted

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Michael A. Greenwood

It took three years of toil, millions of images and a considerable fortune for researchers at the Allen Institute for Brain Science in Seattle to complete a project so vast some doubted its chances of success.

They have mapped the pea-size brain of a mouse.

The research, completed in late September, provides a detailed look at gene activity in the brain at the cellular level. Researchers pinpointed the anatomical location of some 21,000 genes, essentially the entire genome, and also showed in which regions and cells each is expressed. Given that mice and humans share more than 90 percent of genes, the successful mapping of the rodent’s brain has potential implications for the future study of devastating human neurological diseases afflicting millions.

This cutaway view shows a computationally reconstructed 3-D rendering of mouse brain anatomy, with reference planes reflecting a standard 3-D coordinate system through the brain.

The Allen Brain Atlas was produced through a process called in situ hybridization. It shows where each gene is turned on in a series of thin tissue sections. Genes are detected in various sections with a probe specific to each gene. Cells using those genes are then stained and photographed with an automated microscope with a 10x objective lens, and the image is uploaded onto a server. About 85 million images, virtually every nook of the mouse’s minuscule brain, were captured during the meticulous survey. Sixty researchers worked full-time on the project, which carried a price tag of $41 million.

The Atlas is comparable to the Human Genome Project completed in 2003. But the Allen study went one important step further — it shows where the genes are “turned on” in the brain.

This image shows expression of a specific gene, called etv1, in an area of the brain associated with motivation and reward. The color coding reflects the level of gene expression.

And with all of the information — some 600 terabytes, enough data to fill about 20,000 high-capacity iPods — posted on the Internet at no cost, scientists are already delving into the Atlas to advance their own research. The Atlas can shave off months, even years, of redundant work and is expected to further understanding of Alzheimer’s disease, autism, addiction, epilepsy, schizophrenia and Parkinson’s disease. A researcher, for instance, can compare the Atlas brain with others altered to mimic neurological and psychiatric diseases found in humans.

With the project on the mouse brain complete, researchers at the institute plan to switch their focus to questions about the human brain, concentrating on the cortex. The goal is to build an atlas of cell types within the cortex. The institute also will be seeking to collaborate with scientists at other institutions.

Nov 2006
Basic ScienceBiophotonicsBusinessMicroscopyRapidScan

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