It was the day before Christmas, and the normally busy MIT laboratory on Vassar Street in Cambridge was quiet. But creatures have been definitely stirring, together with a mouse that will soon be world famous. Steve Ramirez, a 24-year-previous doctoral pupil at the time, placed the mouse in a small steel field with a black plastic ground. As a substitute of curiously sniffing round, although, the animal instantly froze in terror, recalling the experience of receiving a foot shock in that very same field. It was a textbook concern response, focus and concentration booster if anything, the mouse’s posture was more inflexible than Ramirez had expected. Its memory of the trauma should have been quite vivid. Which was wonderful, because the memory was bogus: The mouse had never obtained an electric shock in that box. Quite, it was reacting to a false memory that Ramirez and his MIT colleague Xu Liu had planted in its mind. "Merry Freaking Christmas," read the subject line of the email Ramirez shot off to Liu, who was spending the 2012 holiday in Yosemite National Park.

The observation culminated greater than two years of a protracted-shot analysis effort and supported an extraordinary speculation: Memory Wave Not only was it doable to identify mind cells involved within the encoding of a single memory, however those specific cells could possibly be manipulated to create an entire new "memory" of an occasion that never happened. "It’s a fantastic feat," says Howard Eichenbaum, a leading memory researcher and director of the center for Neuroscience at Boston College, where Ramirez did his undergraduate work. The prospect of tinkering precisely with memory has tantalized scientists for years. "A lot of individuals had been considering along these strains," says Sheena Josselyn, a senior neuroscientist on the Hospital for Sick Children in Toronto, who research the cellular underpinnings of memory, "but they by no means dreamed that these experiments would actually work. Besides Ramirez and Liu. Their work has launched a brand new period in memory research and could someday lead to new therapies for medical and psychiatric afflictions akin to depression, publish-traumatic stress disorder and Alzheimer’s disease.

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"The sky is admittedly the limit now," says Josselyn. Though the work so far has been carried out on lab mice, the duo’s discoveries open a deeper line of thought into human nature. If reminiscences will be manipulated at will, what does it mean to have a past? If we are able to erase a foul memory, or create a superb one, how will we develop a true sense of self? "Memory is identification," the British author Julian Barnes writes in his memoir Nothing to Be Frightened Of. "I was at all times amazed by the level of management that science can have over the world," says Ramirez, who collected rocks as a kid and remembers being astounded that there truly had been ways to figure out how outdated rocks have been. "The instance is form of banal by now," he says, "but as a species we put someone on the moon. What Ramirez, now 26, and Liu, 36, have been able to see and control are the flickering clusters of neurons, referred to as engrams, where individual memories are saved.

Joining forces in late 2010, a number of months after Ramirez began his graduate work at MIT, the 2 men devised an elaborate new method for exploring living brains in motion, a system that combines classic molecular biology and the emerging area of optogenetics, Memory Wave during which lasers are deployed to stimulate cells genetically engineered to be sensitive to gentle. Armed with state-of-the-artwork tools, and backed by MIT’s Susumu Tonegawa, a Nobel laureate for his work in immunology whose lab they were part of, Ramirez and Liu embarked on a quest that resulted in two landmark studies revealed 16 months apart, again-to-again blasts of brilliance that advanced our understanding of memory at the cellular degree. In the first research, published in Nature in March 2012, Ramirez and Liu recognized, labeled after which reactivated a small cluster of cells encoding a mouse’s concern memory, on this case a memory of an atmosphere where the mouse had received a foot shock. The feat offers strong proof for the lengthy-held theory that reminiscences are encoded in engrams.

Most previous makes an attempt concerned monitoring both the chemical or the electrical activity of brain cells throughout memory formation. Ramirez and Liu rejected those methods as too inexact. As an alternative, they assembled a custom-made set of methods to render mouse brain cells of their goal area (a part of the hippocampus called the dentate gyrus) delicate to gentle. Working with a specialised breed of genetically engineered lab mice, the crew injected the dentate gyrus with a biochemical cocktail that included a gene for a mild-sensitive protein, channelrhodopsin-2. Active dentate gyrus cells-those collaborating in memory formation-would produce the protein, thus turning into gentle-delicate themselves. The thought was that after the memory had been encoded, it could be reactivated by zapping those cells with a laser. To do this, Ramirez and Liu surgically implanted skinny filaments from the laser through the skulls of the mice and into the dentate gyrus. Reactivating the memory-and its related fear response-was the one way to show they had truly identified and labeled an engram.

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Pub: 11 Aug 2025 09:17 UTC

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