We all know the disorienting feeling of realizing we’ve lost a memory—forgetting your best friend’s birthday party from ten years ago, or the road trip you took to Florida as a kid. New research suggests that these memories aren’t really gone for good, they’ve just drifted out of reach.
In a new study, published Wednesday in Nature, scientists from the Massachusetts Institute of Technology managed to retrieve lost memories in mice by zapping their brains with lasers, stimulating their neurons with light. It could lead to new treatments for Alzheimer’s disease, the most common type of brain degeneration, but it also teaches us something new about memories and how they’re stored.
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“Our lab is interested in how we form long-term memories,” said lead author Dheeraj Roy, a fourth-year PhD student in the lab of Susumu Tonegawa, director of the RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory. Roy studies early Alzheimer’s, when memories begin to slip away, but nerve cells haven’t yet begun to rapidly die off. “We’re hoping it will teach us about the components of the brain in normal animals that allow us to form a memory,” he explained.
Scientists already know that a brain region called the hippocampus is important for storing memories, but the next step is finding out which specific neurons are involved. “These big structures in the brain have hundreds of thousands of neurons,” Roy said. “It doesn’t make sense that, for every memory, the entire structure is used. Can we pinpoint a group of neurons that are crucial for one memory?” Once these neurons are found, they could theoretically be targeted with some sort of memory drug, but that will come later.
In this study, Roy, Tonegawa and their team took two groups of mice: one healthy, and another genetically engineered to mimic Alzheimer’s. All the mice were placed in a chamber, where they got a shock to the foot. When they were put back in that same space an hour later, they all showed fear. But several days later, when they went back again, only the normal mice were scared. The mice with Alzheimer’s didn’t seem to remember.
This image depicts a single memory engram cell (green) in the hippocampal dentate gyrus (DG) region of a mouse model of early Alzheimer’s disease. Image: Dheeraj Roy
Using a virus, scientists tagged certain neurons in their brains with a light-sensitive protein, then installed a hollow optic fiber above the area they wanted to investigate. This is a technique called optogenetics, which involves using light to turn neurons on and off.
“We can plug the mice into lasers, and send light into deep parts of the brain,” Roy said, activating specific cells. When these cells were switched on, the mice recalled feeling afraid. The Alzheimer’s mice were put in a room they’d never seen before, as cells coding for the fearful experience were activated. The mice immediately froze, a sign of fear.
It’s a fascinating result, but brain-zapping lasers probably won’t be used to treat memory loss anytime soon. As scientists begin to identify specific neurons that code memories, Roy said, others can work on developing ways to target them, including with drugs. “I think people would be very excited to get similar results,” he said, “without viruses and lasers.”
