Mapping the Mind: Online Interactive Atlas Shows Activity of 20,000 Brain-Related Genes

A meticulously constructed atlas of the human brain reveals the molecular roots of mental illness—and of everyday behavior

THE HUMAN BRAIN IN 3-D In another screenshot to be included in a later iteration of the atlas, a single 3-D view merges structural MRI scans with other imaging data showing the locations of the nerve fiber tracts. Colors separate different subdivisions of the brain’s cerebral cortex, its outermost section. Some nerve fiber tracts are also visible. Such images provide an important anatomical reference on which researchers can overlay information about gene expression. Courtesy of the Allen Institute for Brain Science
TRACTS OF THOUGHT Here, a 3-D rendering of the brain shows the major tracts of nerve fibers spanning its interior, with the colors denoting the directions in which they run: blue fibers run top-to-bottom, red side-to-side and green front-to-back. (Although the nerve fiber data is already available in the online atlas, the viewing tool needed to see the brain in 3-D will appear in future versions of the atlas.) Courtesy of the Allen Institute for Brain Science
MAPPING A MOLECULE FOR MOVEMENT In this screenshot from the Allen Brain Atlas, spots overlaying three MRI snapshots of the brain denote the activity of a gene called ADORA2a implicated in movement disorders such as Huntington’s and Parkinson’s diseases. (The adora2a protein also binds to caffeine.) The color of each spot indicates the extent to which ADORA2a is expressed in that location, with red signifying higher levels and green, lower. The red crosshairs intersect in the basal ganglia, a brain area involved in motor control and in which the gene is strongly expressed. Courtesy of the Allen Institute for Brain Science
CONSTELLATION OF GENES This image from a gene chip shows the activity of thousands of genes from tissue taken from a section of the hippocampus. Each spot denotes activity from a separate, single gene; the brighter the spot, the more active that gene is in the tissue sample tested. Courtesy of the Allen Institute for Brain Science
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GENE CHIPS AT WORK To assess gene expression in each small bit of tissue, researchers expose its RNA to a gene chip, or DNA microarray. These small devices are coated with clusters of identical DNA molecules, called probes, within separate areas. Each probe binds to the RNA of a specific gene—the one that contains a complementary set of chemical units, or bases. In a DNA molecule, the base adenine (A) sticks to thymine (T), and guanine (G) pairs with cytosine (C). Thus, the sequence that would bind to the strand illustrated above is (from top to bottom): T, C, C, T, G, C, A. In this way, a chip records which genes are active, and to what extent they are active, in the tissue sample. Jared Schneidman Design
LASER DISSECTION Researchers view each hair-thin wafer of brain tissue under a microscope outfitted with a laser for precision dissection. The laser cuts short ribbons of tissue about one-millimeter across. Note the white “holes” in this slice from the brain’s hippocampus, a structure involved in memory. Each tissue ribbon is then dropped into a test tube and its RNA purified for gene expression analysis. Courtesy of the Allen Institute for Brain Science
REVEALING ANATOMY Anatomists cut each solidified brain slice into blocks small enough to fit onto a 2 X 3-inch microscope slide, making incisions that skirt key brain structures (left). Staining of a thin sliver of each block can highlight the main bodies of nerve cells (top, purplish image) with the darker areas indicating high cell density near the brain’s surface. A different stain marks nerve cell fibers (bottom), revealing heavy staining in the central region where nerve fiber tracts connect one region of the brain to another. Anatomists use these higher resolution images to sketch out the structural anatomy of the brain in detail. On this anatomical scaffold researchers will overlay information about gene activity—the genes a cell translates into RNA transcripts and then often protein molecules. Courtesy of the Allen Institute for Brain Science
BEEFING UP THE BRAIN A scientist pours a solidifying substance onto the frozen brain (left), so that it maintains its shape and can be easily divided into smaller sections. Removing a layer of white residue smoothes the surface of the slab and reveals its internal anatomy (right). Courtesy of the Allen Institute for Brain Science
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SLICED AND FROZEN Technicians slice the brain as if it were a loaf of bread into slabs up to about a centimeter thick. They place each slab onto a plate that sits on a slurry of dry ice, freezing the neural tissue to preserve it. Courtesy of the Allen Institute for Brain Science
STRIPPING OFF SCAFFOLDING In the first phase of construction, laboratory workers remove the thin, sturdy membrane, embedded with a net of blood vessels, that encases the brain. Stripping the cerebrum of this protective layer allows the brain to be sliced more evenly. Courtesy of the Allen Institute for Brain Science
UNCHARTED TERRITORY Through this web portal, researchers can enter an intricate molecular landscape in which the active genes dot each hill and valley of the human brain. The interactive atlas, called the Allen Human Brain Atlas, is designed to greatly speed scientists’ discovery of the molecular underpinnings of mental illness as well as the intricacies of ordinary human thought and behavior. Allen Brain Atlas data portal: www.brain-map.org