What could that engram actually be?

The answer, previous research suggests, is that brain cells activated by an experience keep one another on biological speed-dial, like a group of people joined in common witness of some striking event. Call on one and word quickly goes out to the larger network of cells, each apparently adding some detail, sight, sound, smell. The brain appears to retain a memory by growing thicker, or more efficient, communication lines between these cells.

The billion-dollar question is how?

In the decades since this process was described in the 1960s and 1970s, scientists have found scores of molecules that play some role in the process. But for years the field struggled to pinpoint the purpose each one serves. The problem was not that such substances were so hard to find — on the contrary.

In a 1999 paper in the journal Nature Neuroscience, two of the most prominent researchers in brain science, Dr. Jeff W. Lichtman and Joshua R. Sanes of Harvard, listed 117 molecules that were somehow involved when one cell creates a lasting speed-dial connection with a neighbor, a process known as “long-term potentiation.”

They did not see that these findings were necessarily clarifying the picture of how memories are formed. But an oddball substance right there on their own list, it turned out, had unusual properties.

A Helpful Nudge

“You know, my dad was the one who told me to look at this molecule — he was a scientist too, my dad, he’s dead now but he had these instincts — so anyway that’s how it all started,” Dr. Sacktor was saying. He was driving from his home in Yonkers to his laboratory in the East Flatbush neighborhood of Brooklyn, with three quiches and bag of bagels bouncing in the back seat. Lunch for the lab.

The father’s advice led the son, eventually, to a substance called PKMzeta. In a series of studies, Dr. Sacktor’s lab found that this molecule was present and activated in cells precisely when they were put on speed-dial by a neighboring neuron.

In fact, the PKMzeta molecules appeared to herd themselves, like Army Rangers occupying a small peninsula, into precisely the fingerlike connections among brain cells that were strengthened. And they stayed there, indefinitely, like biological sentries.