Neuroscientists are exploring previously uncharted territories in the microscopic world of the neuron—observing brain cells while they work, detecting microscopic evidence of Alzheimer's disease in the living brain, and even engaging in some mind reading. The 1990s were touted as the “decade of the brain,” but scientists in the 2000s are examining the living brain with far more fantastic precision.

To study the functions of neurons at the microscopic scale, researchers typically use fine-glass electrodes, but that method cannot provide the precise location of the cells while the animal is alive. The researcher can pinpoint a cell's whereabouts only by injecting it with a chemical marker that can be seen by a microscope once the animal is sacrificed.

Now a new technique—called single-neuron functional imaging—allows scientists to watch brain cells at work while they are still in the brain. Earlier in 2005 R. Clay Reid and his colleagues at Harvard Medical School made time-lapse images using a laser and a microscope that recorded the simultaneous activity of hundreds of neurons in the visual cortex of laboratory cats and rats. The method, which was described in the February 10 Nature, should enable neuroscientists to make architectural maps of brain functions such as vision, movement and learning with single-cell accuracy.

Neuroscientists are not only constructing better maps of the brain, they are taking steps toward reading the human mind. Yukiyasu Kamitani of the ATR Computational Neuroscience Laboratories in Japan and Frank Tong of Vanderbilt University showed that there is a tight coupling between brain states, as measured by functional magnetic resonance imaging, and subjective mental states. Writing in the May Nature Neuroscience, the scientists describe how they were able to predict which one of eight visual patterns a person was looking at by decoding the activity among small groups of neurons in the visual cortex. They believe this type of mind reading can be extended to investigate the neural basis of awareness, memory and other types of “mental content.

Watching the brain do its job is fine when everything is working well, but when disease strikes, scientists would like to look inside to find out what might be causing the problem. Neurologist Bradley Hyman of Massachusetts General Hospital and his colleagues have developed tools that can track microscopic neural changes in a living mouse model of Alzheimer's disease. Using multiphoton microscopy and a fluorescent tracer, the scientists were able to detect the presence of amyloid plaques—a hallmark of the disease—with microscopic accuracy. The scientists are currently exploring a similar method that uses positron-emission tomography to diagnose and study the progress of the disease in humans.

These new techniques allow scientists to catch a glimpse of what is going on in the brain, but another recent development will help them to understand what they are seeing. In the April 22 Physical Review Letters, Nathan N. Urban of Carnegie Mellon University and his co-workers describe a method that enables them to predict how groups of neurons synchronize their activity. Because synchronized activity is the basis for coding and storing information in the brain, their work has broad implications for sorting out how the brain makes the remarkable thing we call the mind.