Can bad memories be changed? In this excerpt from “How to Change Your Memory” (Princeton University Press, 2025), the author and neuroscientist Steve Ramirez It describes the events that led him and his colleagues to discover memories. Rodents can be artificially controlled by directly tapping their brains.
Our biology often forces us to prepare for a variety of outcomes amid uncertainty. Paying attention to these different outcomes is healthy because it encourages us to prepare and work appropriately for any given stressful event. However, sometimes the stress scale tips so far that brain pathology begins to manifest itself.
For example, the enormous variation in how individuals reach states of anxiety highlights that our brains contain many winding paths that can ultimately converge on the same emotion. We all have triggers in life, but those triggers are based on experiences, or memories. When these differences impair our mood, thinking, behavior, and overall daily functioning, they are lumped into one category. Moreover, if the observed disorder shares similar characteristics, this category itself falls under a broader classification, namely mental disorders.
As I entered my final year of graduate school, I began to understand how widespread feelings of anxiety were. Stressors in my life were starting to pile up. Finishing papers, writing grants, filling out job applications, and seemingly constantly pursuing my purpose as a scientist and as a human being. My mother also suddenly had recurrent moments of anxiety, which eventually led to frequent panic attacks. After learning about her lifelong experience with the vagaries that anxiety is to her, I began to understand the nature of these feelings repeating, repeating, repeating. “I couldn’t stop thinking about her panic attacks and how frustrating it was to not be able to press.”turn off” At the most debilitating moment a person can endure.
My final project in graduate school was an attempt to artificially activate positive memories to suppress symptoms associated with anxiety and depression. It will be my most personal scientific endeavor, and a very direct way to thank my mom for joining the fight by her side and being my superhero. If my research can inspire new treatment strategies that may be useful in alleviating these kinds of debilitating conditions, my work will gain a much deeper, more personally meaningful purpose.
My lab partner Xu Liu and I wanted to take a brain-centric approach to our latest project. Is it possible to artificially control memory itself in rodents, in the name of therapeutics, by directly tapping the brain to restore neural and behavioral balance?
Luckily, our project had scientific precedent in humans. influential papers psychologist Barbara Frederickson And what my colleagues called the “cancellation effect of positive emotions.” This study highlighted the ability of positive emotions to undo the physiological effects negative emotions have on the brain and body.
The undo hypothesis suggests that positive emotions can be used for more than just feeling good. It may help you get out of bed in the morning. Pursue happiness; Change the way we think about and interact with ourselves and others. Counteract, or at least regulate, negative emotions. When human subjects watched movie clips that evoked satisfaction and pleasure after a period of stress, their bodies rebounded in beneficial ways. For example, stress-induced increases in cardiovascular activity returned to baseline more quickly than when watching neutral or sad movie clips. Interestingly, this shows a very real physical connection between positive emotions and their direct impact on our biology.
Xu and I wanted to take this research further by starting with biology from the inside out and testing the potential therapeutic power of positive memories. brain. We placed the animal in a box with two small valves on different ends. One delivered sugar water as the animal licked the sugar, and the other delivered plain water. This is known as the sucrose preference test. Rodents generally prefer sugar water to plain water. Likewise, humans generally prefer sugary liquids over smooth liquids. On the other hand, rodents exhibiting depression- and anxiety-related behaviors tend to show a 50:50 preference. They have no preference at all.
As expected, animals exhibiting anxiety- and depression-related behaviors randomly licked each valve over a period of 15 minutes. likewise project — The first successful attempt at MIT to artificially control memories in a rodent brain — all we had to do was turn on the laser and press a button to optogenetically wake up the memories inside.
Click.
A deep blue laser flashed across the rat’s hippocampus, waking it up. — Cells that maintain positive memories. I remember thinking that our optogenetic stimulation was a high-tech Proustian madeleine that could evoke rich memories of the past. If you’ll indulge my romanticism about the moment, the rat immediately perked up, as if a shiver ran from its brain to its body, and began scanning its environment to decide which valve to visit first.
Something amazing was happening. I imagine the mouse felt the memory invading all of his senses, strangely detached, with no hint of its origin. to The mouse is that much was mouse. With the positive memory fully revealed within seconds, the now motivated rats inspected each valve by smell and then taste test.
The key to reversing abnormal behavior has always been found in positive memories.
When they discovered the valve filled with sugar water, the rats began licking vigorously, thus consuming as much sugar water as our control animals. In less than an hour, Xu and I saw that reactivating positive memories restored the mice’s behavior to healthy standards. Similar to reactivating interesting and positive memories, several areas of the brain associated with rewarding experiences and motivation are also activated.
The key to reversing abnormal behavior has always been found in positive memories. While the laser glowed sapphire light in the brain, the rats were motivated to continue consuming sugar water as a reward. All of this happens by stimulating cells in the hippocampus. Or, to say this with a less novelty flare, the rat received a sweet treat.
Next week one of my talented undergraduate students Briana Chen She collected a large empirical data set for the project, and there was an interesting plot twist. When she artificially reactivated positive memories twice a day, or “chronically,” for about a week, it not only permanently improved but also accelerated symptoms she believed were associated with depression and anxiety. Growth of new cells in the brain. Positive memories have both short-term and long-term benefits, from cells to behavior.
Inspired by: Neurocentric research area criteria Through the brain therapy approach of (RDoC), we hoped that the biological efficacy of drug-like positive memories could inform cognitive-behavioral approaches to the treatment of brain disorders. This project was meaningful to me on a personal level. I thought about my mom’s panic attacks and the thought that she would never have to experience the kind of severe anxiety that robs someone of their peace.
Positive memories are one of the most powerful biological tools available to our brains. At home, my mom and I shared the treasure. One memory we both remember was when I was a teenager visiting my mother’s parents in El Salvador.
One morning, my cousins, my parents, and my grandparents all went down the hill behind the house where my mom grew up and went for a swim in the village pond. My cousins kept urging me to jump off the cliff into the pond, and my mom kept telling me there was no need to do that.
Like her, I was the exact opposite of an adrenaline seeker. Because as the words “Please don’t free fall to Earth” kept repeating in my head, my innate biology might have been on to something. She knew I was scared and after a few minutes she suggested we jump together. Surprisingly, she said: We’ll hold hands and tiptoe to the edge — no way, of, three — We were in the air! A moment later, we emerged from the water, laughing cheerfully and in disbelief at our newfound courage.
Neuroscience tells us that these memories contain all the ingredients for life’s dessert that makes us feel good. From an RDoC perspective, my cognitive and valence systems both interact to produce wealth from this experience. The cognitive system enables the memory of jumping off a cliff, which initially generated fear through the negative valence system, now countered almost immediately with a rewarding emotion through the positive valence system.
What was once a moment of fear has now become a memory of triumph with my mom. Because it’s the only time we can remember when both of us literally took a leap of faith, we cherish that memory as an example of what our brains can accomplish together. A million little life moments like these become the good things in life, neatly packaged into a million memories we hold on to.
Adapted from “How to Change Your Memory: One Neuroscientist’s Quest to Change the Past”. Copyright © 2025 Steve Ramirez. Reprinted with permission from Princeton University Press.
