What's in a brain? Neurons, chemical messengers, electric signals—and a lot of empty space. The space between cells takes up a fifth of the volume inside our brains. And although all our thoughts and mental functions traffic through this vital region, scientists are just beginning to unlock its secrets.

Neurobiologists Charles Nicholson of New York University and Eva Syková of the Institute of Experimental Medicine in Prague have developed ways to probe the unseen intercellular space in the brain. By injecting tracers and tracking their diffusion through the living brains of rats and other animals, they have discovered that about 20 percent is extracellular space, filled with cerebrospinal fluid—the same liquid that surrounds and cushions the brain and spinal cord. Nicholson and colleagues also found that diffusion is slow because the many nooks and crannies between cells impede the flow of molecules as they enter microscopic blind alleys and become trapped. Through this pattern of diffusion, chemicals released by nerve cells build up to higher concentrations, which improves communication between neurons.

Syková and her colleagues are studying the way extracellular space changes with disease and aging. Conditions producing a lack of oxygen, such as stroke, shrink the extracellular space. As the space constricts, the diffusion of substances between cells slows, and toxic substances are concentrated, impeding recovery. Aging has the same effect, and the shrinkage may be linked to learning. When Syková compared elderly rats that were fast learners in a maze test with their slower-learning peers, she found that the quick learners had lost much less extracellular space.