The Maestro of Memory Manipulation
Emily Singer writes in Quanta:
ailed 30-year-long quest launched Sheena Josselyn on her current career path. As a psychology major in college, Josselyn, now a neuroscientist at the University of Toronto, had studied the work of Karl Lashley, a famous psychologist who theorized that memories are stored in a collection of brain cells that fire in a certain pattern, known as an engram. The basic idea is that the brain stores a memory — the Seinfeld theme song or the scent of your mother’s perfume — by strengthening the connections among a specific set of neurons. When the brain recalls that memory, the cells fire in the same pattern.
Lashley hoped to prove the engram’s existence by demonstrating that selectively destroying bits of brain tissue would eradicate specific memories. But despite decades spent carefully poking around in the rodent brain, Lashley never managed to localize memory. In 1950, he admitted defeat, proposing instead that memories were not contained within a small set of cells but distributed across the brain.
Josselyn thought of Lashley’s lengthy quest when she was a postdoc at Yale in the 1990s, puzzling over the result of an experiment in mice. She had tinkered with some cells in a part of the brain known as the amygdala, which is tied to emotional memory. Though she had only altered a few cells, the treatment dramatically improved the animals’ memory. These mice were much better at remembering a scary incident — a tone paired with a shock — than their untreated counterparts.
Josselyn began to suspect that she had stumbled upon Lashley’s engram, but it took her nearly ten years to come up with real proof. In 2009, her team demonstrated that they could erase a specific memory in mice by killing a certain set of cells. More than a century after Lashley began his search for the engram, Josselyn finally found it.
The key to her team’s success was a set of molecular tools designed to mark the brain cells that formed a new memory — the neurons that fired when the mice learned that a specific sound predicted an imminent electric shock. The researchers then used these molecular tags to wipe out only those brain cells, eradicating that memory but leaving others intact.
Since then, researchers have used these and other tools to toy with the engram in ever more sophisticated ways. They can silence or activate the cells that make up the memory’s pattern, erasing and evoking specific memories and even implanting false memories.
The power to control memory is both exciting and frightening. It evokes the dark images of science fiction movies such as Eternal Sunshine of the Spotless Mind, in which a couple erases painful memories of each other. But the research also has the potential to unlock the mystery of memory disorders such as post-traumatic stress disorder (PTSD), perhaps leading to new treatments.
Josselyn is now trying to unpack the engram’s molecular nuts and bolts, which she hopes will spark development of new therapies for addiction, Alzheimer’s disease and other illnesses. Quanta Magazine recently spoke with Josselyn about her search for the engram. An edited and condensed version of that conversation follows.
QUANTA MAGAZINE: What is an engram?
SHEENA JOSSELYN: It’s the physical manifestation of a memory in the brain, a collection of cells that, if we activate them, express a memory. It changes when we learn something and fires again when we recall something.
How does the brain create an engram? . .