Marilyn Monroe and Jane Russell appeared outside Grauman’s Chinese Theatre to write their names and leave imprints of their hands and high heels in the wet concrete. Down on their knees, supported by a velvet-covered pillow for their elbows, they wrote “Gentlemen Prefer Blondes” in looping script, followed by their signatures and the date, 6-26-53. But how did those watching the events of that day manage to imprint a memory trace of it, etching the details with neurons and synapses in the soft cement of the brain? Where and how are those memories written, and what is the molecular alphabet that spells out the rich recollections of color, smell, and sound?
After more than a century of searching, an answer was recently found, strangely enough, just eight miles from Grauman’s. Although not located on any tourist map, the scene of the discovery can be reached easily from Hollywood Boulevard by heading west on Sunset to the campus of UCLA. There, amid one of the densest clusters of neuroscience research facilities in the world, stands the Gonda (Goldschmied) Neuroscience and Genetics Research Center. And sitting at a table in the building’s first-floor restaurant, the Café Synapse, is the neuroscientist who has come closer than anyone ever thought possible to finding the place where memories are written in the brain.
That spot, the physical substrate of a particular memory, has long been known in brain research as an engram. Decades of scientific dogma asserted that engrams exist only in vast webs of connections, not in a particular place but in distributed neural networks running widely through the brain. Yet a series of pioneering studies have demonstrated that it is possible to lure specific memories into particular neurons, at least in mice. If those neurons are killed or temporarily inactivated, the memories vanish. If the neurons are reactivated, the memories return. These same studies have also begun to explain how and why the brain allocates each memory to a particular group of cells and how it links them together and organizes them—the physical means by which the scent of a madeleine, the legendary confection that sparked Marcel Proust’s memory stream, leads to remembrance of things past.
“It’s amazing,” says neurobiologist Alcino Silva, codirector of the UCLA Integrative Center for Learning and Memory. “For the last hundred years, scientists have been looking for the engram in the brain. We have now gotten to the point that we know enough about memory and how memories are formed that we can actually find the engram, and by finding it, we can manipulate it.”
The work recalls the movie Eternal Sunshine of the Spotless Mind. But unlike that film, in which the characters played by Jim Carrey and Kate Winslet have their memories of each other fully erased, Silva and other researchers involved in the manipulation of engrams do not believe that they can wipe clean every bit of a memory, only certain parts. Targeting the amygdala, the almond-shaped region in all mammals where fear memories are stored, Silva and his colleagues have shown that they can largely eliminate a mouse’s fearful response to a tone the animal had previously learned to associate with an unpleasant electric stimulus. Whether the mouse still remembers having heard the sound is uncertain, but the animal demonstrably no longer remembers the lesson it learned—that this particular tone was a prelude to getting zapped.
