Scientists have captured the first images of brain cells making long-term connections in response to the kind of stimulation thought to underlie memory formation. "Long-lasting, durable memories that arise upon repeated stimulation [were] postulated to involve a visible change in these connections," Yukiko Goda of the University of California in San Diego explains, "but it had been quite controversial." The report describing these results appears in the current issue of Cell.

The leading model for how neurons connect to make memories assumes that a cell has to be prodded repeatedly to form a lasting connection, or synapse, with another cell. In an analogous way, Goda says, a student may remember something for a short time by cramming the night before a test, but only reviewing the material will make it stick.

To catch the process of synapse formation in action, Goda and colleagues engineered nerve cells to produce a fluorescent form of the actin protein, which provides a cell with structural support. The team grew these cells in culture on top of a silicon wafer. Shining light from a microscope onto a single cell caused electricity to flow through the illuminated silicon and excited the cell¿much like one neuron stimulates another. After a single exposure to the spotlight, actin crept toward spots that touched adjacent neurons, but soon receded. When the cells received four exposures over an hour, however, the actin moved into these junctions and stayed for up to 18 hours, suggesting that synapses had formed. "What we see shows all the hallmarks of a synapse," she notes.

The next step, Goda says, will be to follow the nerve cells longer to see if the connections last. "But the exciting part is that now we can induce these sorts of changes and ask, 'What is the molecular machinery that underlies this [process]?'" When that's done, she adds, researchers can disrupt the mechanism in animals and see what happens.

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