Has a familiar tune, a photograph or a distinct scent ever transported you back to a memory complete with all the sensations of the experience? Researchers at MIT have sought to learn whether these memory traces, known as memory engrams, are conceptual or whether they are a physical network of neurons in the brain. Using an optogenetic technique that uses light to target specific populations of neurons in the brain, the scientists made mice recall fear memories and respond by freezing. “Our results show that memories really do reside in very specific brain cells and [that] simply by reactivating these cells by physical means, such as light, an entire memory can be recalled,” said Xu Liu, a doctoral student in the lab of lead author Susumu Tonegawa. “We demonstrate that behavior based on high-level cognition, such as the expression of a specific memory, can be generated in a mammal by highly specific physical activation of a specific small subpopulation of brain cells – in this case, by light,” said Tonegawa, the Picower professor of biology and neuroscience at MIT. The scientists first identified a specific set of brain cells that become activated in the hippocampus when the mouse forms a new memory. They determined which genes were activated in those cells and coupled them with the gene for channelrhodopsin-2 (ChR2), a light-activated protein used in optogenetics. They studied the mice with this genetic couplet in the cells of the dentate gyrus of the hippocampus using tiny optical fibers that delivered light pulses to the neurons. They observed that the light-activated protein was expressed only in the neurons involved in experiential learning, which allowed for labeling of the physical network of neurons associated with a specific memory engram for a specific experience. The mice were placed into an environment to explore and, after a few minutes, received a mild foot shock, learning to fear the particular environment in which the shock occurred. The brain cells activated during this fear conditioning became tagged with ChR2. Later, when the scientists exposed the mice to triggering pulses of light in a completely different environment, the neurons involved in the fear memory switched on, and the mice quickly entered into a defensive, immobile crouch position. The light-induced freezing suggested that the animals actually recalled the memory of being shocked and perceived this replay of a fearful memory – but the memory was artificially activated. “We wanted to artificially activate a memory without the usual required sensory experience, which provides experimental evidence that even ephemeral phenomena, such as personal memories, reside in the physical machinery of the brain,” said co-author and graduate student Steve Ramirez. The method also may have applications in the study of neurodegenerative and neuropsychiatric disorders. “The more we know about the moving pieces that make up our brains, the better equipped we are to figure out what happens when brain pieces break down,” Ramirez said. The work was published online March 22 in Nature (doi: 10.1038/nature11028).