THE BRAIN AGLOW: This image shows a section of mouse cerebellum labeled using the Brainbow3 technique in which fluorescent markers are randomly expressed in membranes of cells. Purkinje cell bodies (green), sprouting their typically dense, tree-like dendrites, are surrounded by several inhibitory basket cell neurons (white arrows).COURTESY OF D. CAI, JR SANES, JW LICHTMAN HARVARD U.How are all the neurons in the brain connected? Large initiatives in the U.S. and Europe have been pouring tens of millions of dollars into answering this question. What’s driving the effort to create comprehensive maps of neuronal connections is the hope that scientists will be able to glean from them the physical basis of perceptions and behaviors—and to develop anatomical signatures of brain disorders.
Connectivity studies are using a variety of imaging approaches to examine circuits at different scales. For example, diffusion magnetic resonance imaging, while unable to resolve individual synapses (which measure about 20 nm in width), is being employed to plot long-range connections throughout the brain. At the other extreme, electron microscopy–based methods show synapses in great detail, though this approach is time-consuming and spatially limited. Light microscopy approaches fall in between, allowing researchers to quickly examine larger areas. But light microscopy methods cannot typically resolve cell features, such as synapses, whose sizes are less than the wavelength of light used—effectively about 250 nm. (For techniques that combine light- and electron-microscopic examination of the same sample, see “Seeing Double” here.)
In the past few years, new strategies ...
