Imagine if, with the flip of a switch, memories stored in the brain could flick on and off—an argument with your mother, for example, or the smell of a particular summer day. Scientists at MIT reported Thursday that they have accomplished something like that, activating brain cells and conjuring a remembrance of time past with a beam of light.
The feat is basic research in mice and far from even being tried in a person, but it is a powerful demonstration that memories reside in specific cells in the brain and that they can be turned on. The work, published in the journal Nature, gives scientists a way to explore myriad questions, from how memories are preserved and recalled to how they can erode over time.
“To my mind, turning on a memory is a really cool, cool step. To be honest, I never thought this would work—it’s like the dream experiment. You fall asleep thinking about it,” said Sheena Josselyn, a senior scientist at the Hospital for Sick Children in Toronto who was not involved in the research.
“The next step can be just about anywhere,” Josselyn said. “Say they have a mouse model of Alzheimer’s and want to keep the memory alive. Maybe if you stimulate the memory, they won’t ever forget it. Maybe you can stimulate a good memory when something is horrible.”
The work was led by Susumu Tonegawa, a professor of biology and neuroscience at the Massachusetts Institute of Technology and a Nobel laureate who leveraged a powerful, new tool in neuroscience called “optogenetics.” By adding a gene that carries instructions for a light-sensitive protein to specific brain cells and then threading a fiber-optic cable into a mouse’s head, researchers have been able to trigger various behaviors with light, including causing a mouse to run in a circle or quelling anxiety.
Tonegawa and colleagues, including Stanford University neuroscientist Karl Deisseroth, who pioneered the use of light and genetic manipulation to activate brain circuits, decided to try out the technique to activate memories.
Even something as intangible as a memory must be physically stored somewhere in the brain, but identifying and definitively activating that information had been difficult. In the 1900s, neurosurgeon Wilder Penfield mapped the human brain and found that when he electrically stimulated parts of the brain, subjects would sometimes report being reimmersed in past experience.
But to definitively show how memory is stored, and to force its retrieval from a subset of cells, took painstaking work and a new, precise technique for activating brain cells.
Researchers chose to test a simple kind of memory—a fear memory. In one experiment, mice were put in a chamber, allowed to explore, and given a foot shock. The next time the mice were put in the same dangerous chamber, they remembered the unpleasant electric shock and froze, taking on a defensive stance. Researchers had, however, inserted a gene that codes for a light-sensitive protein into the cells involved in making a memory. They then tested what happened when they turned on a light to activate those cells, without putting the mice in the same chamber. They saw the freezing behavior, as if the mice were reliving the memory.
“This is the most dramatic way to show that high cognitive phenomenon, like memory recall, can be generated, can be artificially generated by poking cells in the brain,” Tonegawa said in an interview.
He said there were about 20,000 neurons, or brain cells, involved in this particular kind of memory.
Tonegawa said his lab is interested in examining other types of memory—for habits that can underlie addiction, for example—and in finding ways to probe long-term memories. Different types of memories will be distributed in various spots and networks around the brain, he said, and he wants to map these basic circuits.
He is also exploring how the nature of what is being remembered matters—his research shows already that memories of similar events seem to involve overlapping groups of cells, while memories of distinct events are stored in different groups of cells.
“Even under normal conditions,” Tonegawa said, “how we can distinguish various events, various experiences and be able to reproduce it later, is of course a very interesting question, and I think one that we face in day to day life.”