New method captures brain cells in action

For years, researchers could examine nerve cells just one at a time, and were unable to see how they interacted.

But Harvard Medical School researchers, in a paper published last week, said that they have finally captured confetti-like clusters of the cells in action. They have tested rats and cats.

Eventually, researchers hope to use their new technique to map the outer, nerve-dense layer of the brain. That would help solve one of the greatest questions of neuroscience -- how a normal brain functions and how it changes with age or disease.

"The brain works with neurons, and neurons are part of a circuit. In order to understand how a circuit works, we need to find out where the neuron is, and what does it do," said Clay Reid, a Harvard neurobiologist who coauthored the work that appeared in the journal Nature. "We're not going to be able to understand how it's broken" until we understand how it works.

The researchers already have been able to refine a long-held theory: Neurons were thought to be arranged in rough columns depending on the job they did. Reid and colleagues found the cells are actually laid out with incredible precision, almost like crops in a field, with rows of nerve cells that sense upward motion next to ones that sense downward motion.

That idea originated decades ago just down the hall from Reid's office. Torsten Wiesel and David Hubel won the Nobel Prize for their pioneering work on the brain's organization, but Reid's work illuminates that organization at an unprecedented scale.

By combining two kinds of imaging methods, Reid and colleagues have found a way to isolate the activity of single nerve cells and tested their technique on the visual circuits of rats and cats. He predicted a "gold rush" as brain researchers use similar techniques to map individual nerve cells responding to different kinds of stimuli.

While advances in brain-imaging technology have created powerful diagnostic tools for use in hunting down strokes, seizures, and brain tumors, the MRI and CT scans commonly used in hospitals yield only limited information about how different parts of the brain are coordinated.

"What many neuroscientists are trying to understand is how does the brain work. We think it depends on local circuitry," said Alan Jasanoff, a neuroscientist from the Massachusetts Institute of Technology. Research techniques thus far have been able to illuminate the activity of just a few nerve cells because such monitoring traditionally involved the painstaking process of injecting a dye directly into individual cells.

Reid and his colleagues have combined both worlds, by capturing the activity of a region about the size of a single pixel on a normal brain scan and using a special dye and laser beam that illuminates cells in action. Other researchers said they were excited by the potential of the new technique. "The big potential for the advance is you could selectively study cells of a single type," New York University neuroscientist Paul Glimcher wrote in an e-mail. "That would be super cool."

Carolyn Y. Johnson can be reached atcjohnson@globe.com.