Two Neuroscientists Envision A ‘Repair Shop’ For The Brain
In “How to Change a Memory,” neuroscientist Steve Ramirez embarks on a project to find and reactivate memories in the brains of mice.
The following is an excerpt from How to Change a Memory: One Neuroscientist’s Quest to Alter the Past by Steve Ramirez.
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How to Change a Memory: One Neuroscientist's Quest to Alter the Past
May 26, 2011 might have been a sunny day in Boston, perfect for a brisk jog along the Charles River. Or it might have been a gloomy day, just right for a pint and a movie in Harvard Square. It could have been the ideal day for baseball if the Red Sox were back in town. But I can’t tell you for sure. I can’t tell you what I had for breakfast, lunch, or dinner that day. I can’t tell you who I called, what news I read, what music I listened to. There are bits of experience I don’t remember because, well, I’m relying on my memory.
And yet, somehow, I do remember that I was in a windowless dark room at the Brain and Cognitive Sciences building at MIT that afternoon, transferring a small, black mouse from the palm of my hand into an almond-scented box about the size of a milk crate, with white floors, transparent walls, and a camera mounted overhead.
The mouse began sniffing its surroundings. It was no stranger to the box, having investigated the same corners just yesterday. The fact that nothing monumental had occurred during its initial journey in the box was important: it meant that the mouse had no reason to be afraid this time around. It could go about its business without fear as I recorded its behavior with my lab partner, Xu Liu.
Ten days earlier, I watched as Xu anesthetized this very same mouse. We both felt similarly regarding the lab mice we worked with: we approached them with veneration for their biological revelations and with tremendous care for the life that they experience. Xu in particular took this relationship seriously, and that day I could tell how much this dynamic meant to him as he carefully lowered two glass barrels into two small holes through the top of the skull of the mouse. Like miniature flashlights, about the width of cocktail straws and shorter than the nail on your pinky finger, these glass barrels are capable of funneling and focusing light onto the part of the mouse’s brain in which they are nestled—in this case, in the mouse hippocampus. Why did we want to shine light onto the mouse’s hippocampus though? As part of our experiment, we’d made this particular mouse special using some genetic trickery called optogenetics. Put succinctly, optogenetics entails hand-crafting special bits of DNA that make a cell light-sensitive, and delivering those bits into very specific cells into the brain. Once these brain cells are made light sensitive, researchers can turn them on or off with light, much like a switch. Xu and I planned to focus beams of light directly onto our light-sensitive cells in the hippocampus, and voilà, those cells would turn on. It’s these particular hippocampus cells, we hypothesized, that contained a memory.
Based on what we knew about the inner workings of the brain, Xu and I had every reason to believe that the hippocampus is like a mental time machine: an area that is active when a mouse is trying to remember the shortest path to return to the tasty crumbs in the kitchen pantry, or in one of us humans, when you recall the memory of your first kiss, or hearing your baby coo for the first time, or last Friday’s delicious steak frites dinner. The hippocampus contains millions of brain cells, which chunk space and time into our personally experienced events. The hippocampus, in short, is crucial to the process of memory, in both our mouse and in humans. It teleports us to relive the past.
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Xu and I were playing with an idea that day in the lab, as our mouse scurried about its box: Could we “turn on” a memory if we triggered the parts of the brain where it lived?
We were in essence testing a hypothesis first put forth over one hundred years ago by the German zoologist Richard Semon. Semon proposed that memories are a kind of lasting physical imprint, or “trace” in the brain—somehow, the marvelous waters of memory carve measurable grooves in the neural riverbeds of the brain. For the savvy enthusiast, there’s an official term for this so-called memory trace, and it was first proposed by Semon himself: engram.
The holy grail of memory neuroscience, the engram is thought to be the key to unlocking the power of our brain’s mental time machine. Once we find the engram, Semon’s prescient idea goes, we could probably find a way to reverse engineer memory and, ultimately, control it.
Xu and I used to refer to memory researchers as the auto-mechanics of the brain, taking apart the fleshy machine between our ears one piece at a time in an attempt to understand what each piece does and how it enables our smooth mental time-travel. “If you can break it and make it, then you can understand it,” he’d say.
By 2011, memory researchers had already done just that. They had discovered that it was possible to “erase” memories—to “break” them. If scientists could do that, well, why couldn’t we find memories and reactivate them instead? Breaking something lets us know how it works by preventing some output from happening, Xu and I reasoned, but if we could manually recall a memory—if we could stimulate this same output—then we could get the mental time machine to run again … and again and again at will.
Our goal was initially nonscientific in its basis: we’d break into and jump-start the brain’s time machine. The project had a name in the lab, one that we felt had a mysterious grandeur to it: Project X. It all sounded pretty sci-fi to us, and that was exactly what hooked us in. The idea of activating a memory? Very Total Recall with a bit of Inception thrown in. We felt like kids again, and our playground was the science lab. Sometimes an idea for an experiment just feels “too important and too damn cool not to do,” we’d say.
We thought activating cells that held onto a memory would cause a domino effect in the brain that ultimately led to recollection of that memory. After all, external stimuli in the world do this to us all the time: walking past a bakery and smelling the maple bacon doughnuts might remind you of the last time you cheated on your diet; the sight of a particularly unfashionable shirt at the mall might remind you of an ugly Christmas sweater party with the family; the smell of tequila might re-mind you of that time you dulled your grief with alcohol and woke up in even more pain the next morning. These sights and sounds and smells force us to relive the worlds of the past. They bring engrams back to life.
We just wanted to bypass the external stimuli.
Say that Xu and I were able to reactivate a memory. What next? One of the central goals of doing this kind of science is to discover fundamental truths about how the brain works and to use these truths to help people. Our biggest ambitions for our work included applying a new understanding of the mechanics of memory to treat disorders of the brain. We wondered if we could one day suppress a negative memory to prevent the debilitating effects of PTSD, or toggle down a bout of overwhelming anxiety to prevent a panic attack. If we could activate a memory, then we could think of memory as something our brain naturally produces as well as a potential antidote that the brain contains to rid itself of suffering. The possibilities would be endless: What if we activated positive memories to curb symptoms of depression, or what if we brought a memory back that was thought to be lost to Alzheimer’s, or what if we could etch in entirely new memories to produce a cognitively enhanced brain? All of these possibilities relied on one thing—the ability to control memory, which was what Xu and I had within reach.
Given how far the field had already come, we thought a repair shop for the brain wasn’t all that far-fetched.
Excerpted from HOW TO CHANGE A MEMORY: One Neuroscientist’s Quest to Alter the Past © 2025 by Steven Ramirez. Reprinted by permission of Princeton University Press.