Can bad memories be changed? In this excerpt from How to Change Your Memory (Princeton University Press, 2025), author and neuroscientist Steve Ramirez describes the events that led him and his colleagues to discover that they could artificially control memory by accessing rodent brains directly.
In our biology, we often have to prepare for multiple outcomes in the midst of uncertainty. Worrying about these multiple outcomes is healthy because it encourages us to strive and prepare properly for certain stressful events. However, sometimes the balance of stress tips to the extreme, and brain pathology begins to appear.
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For example, the vastly different ways individuals arrive at anxiety states highlights that our brains have many winding paths that can ultimately converge on the same emotion. We all have triggers in our lives, but what those triggers are are determined by our experiences, our memories. When these differences impair our mood, thinking, behavior, and overall functioning in daily life, they are lumped into one category. Furthermore, if the observed disorders share similar characteristics, this category itself falls into a broader classification, namely the category of mental disorders.
As I was entering my final year of graduate school, I was just beginning to understand how ubiquitous feelings of anxiety were. Just as the stressors in my own life began to accumulate: finishing papers, writing grant and job applications, continuing the never-ending quest to find purpose as a scientist and as a human being, my mother’s moments of anxiety suddenly returned, eventually leading to frequent panic attacks. After learning about her lifelong experience with the unsettling nature of anxiety, I began to understand the recurring nature of these feelings. I couldn’t stop thinking about her panic attacks. And I couldn’t help but think about how frustrating it was to not be able to press “off” during the most debilitating moments a person can endure.
My final project in graduate school was to try to artificially activate positive memories to suppress symptoms related to anxiety and depression. It’s the most personal scientific endeavor for me, and a very direct way to thank my mother for joining the fight and being my superhero. If my research can somehow inspire new therapeutic strategies that may help alleviate such debilitating conditions, then my research will acquire a deeper, more personally meaningful purpose.
My lab partner Xu Liu and I wanted to take a brain-centered approach to our latest project. Is it possible to artificially control rodent memory itself by directly accessing the brain and restoring neural and behavioral balance in the name of therapy?
Fortunately, our project had scientific precedent in humans: an influential paper by psychologist Barbara Fredrickson and colleagues called “The Cancellation Effect of Positive Emotions.” This study highlighted the ability of positive emotions to reverse the physiological effects that negative emotions have on the brain and body.
The undoing hypothesis proposes that positive emotions can be used for more than just feeling good. It can be used to help you get out of bed in the morning. pursue happiness. Change the way you think about and interact with yourself and others. And counteract or at least regulate negative emotions. When human subjects experienced stress and then watched movie clips that elicited feelings of satisfaction and entertainment, their bodies recovered in beneficial ways. For example, stress-induced increases in cardiovascular activity returned to baseline faster than when watching neutral or sad movie clips. Interestingly, this reveals a very real physical connection between positive emotions and the direct impact they have on our biology.
Xu and I wanted to take this research further by activating the biology of positive memories from within the brain and testing the therapeutic potential of positive memories. We placed the animals in a box with two small valves at each end. One delivers sugar water when the animal licks it, and the other delivers regular water. This is known as the sucrose preference test. Rodents usually prefer sugar water to plain water. This is similar to how humans prefer sweet liquids to bland liquids. Rodents with depression- and anxiety-related behaviors, on the other hand, tend to show a 50:50 preference. They show no preference at all.
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As expected, animals that exhibited behaviors associated with anxiety or depression licked each valve randomly over a 15-minute period. As with Project
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The azure laser flashed across the mouse’s hippocampus, awakening and activating cells that held positive memories. I remember thinking that our optogenetic stimuli were fancy, high-tech Proustian madeleines that could evoke rich memories from the past. If you enjoy my romantic rendition of this moment, the mouse immediately perked up, as if a shiver went from its brain to its body, and began scanning its environment to decide which valve to visit first.
Something unusual was happening. I imagine that the mouse felt the memory invade all its senses, strangely disconnected and without any hint of its origin. Because the essence of these sensations was both the mouse and the mouse. Then, once the positive memory was fully revealed within seconds, the motivated mice inspected each valve while sniffing, followed by a taste test.
The key to reversing abnormal behavior was long embedded in their positive memories.
When the mice found the bulb containing the sugar water, they began licking vigorously, ingesting the same amount of sugar water as the control animals. Within an hour, Xu and I saw that reactivating positive memories returned the mice’s behavior to a healthy baseline. When exciting, positive memories are reactivated, many areas of the brain associated with rewarding experiences and motivation are also activated.
The key to reversing abnormal behavior was long embedded in their positive memories. As long as the laser illuminated the sapphire glow in their brains, the mice were motivated to continue ingesting the sugar water as a reward. All of this happens by stimulating cells in the hippocampus. In less novel terms, the mice were given sweet treats.
Over the next few weeks, one of my talented undergraduate students, Briana Chen, collected a large empirical dataset for this project. And it came with an exciting development. When she artificially reactivated positive memories twice a day, or “chronically” for about a week, this not only permanently improved symptoms thought to be related to depression and anxiety, but also stimulated the growth of new cells in the brain. Positive memories had both short-term and long-term benefits, from cells to behavior.
Inspired by the neurocentric Research Domain Criteria (RDoC) approach to treating the brain, our hope was that the biological efficacy of drug-like positive memories could inform cognitive-behavioral approaches to treating brain disorders. This project was meaningful to me on a personal level. I thought about my mother’s panic attacks and thought that maybe she didn’t have to go through the kind of anxiety that takes away someone’s peace.
Positive memories are some of the most powerful biological tools available to our brains. At home, my mother and I shared a treasure trove of them. We both remember 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 mother grew up to swim in the village pond. My cousins encouraged me to jump off the cliff into the pond, and my mother kept telling me that there was no need to do that.
Like her, I was the opposite of an adrenaline seeker. Maybe my innate biological traits were somehow catching on. Because the words “Don’t free fall to Earth” kept repeating over and over in my head. She could sense that I was scared and after a few minutes, to my surprise, she suggested we jump together. We tiptoed to the edge hand in hand – unos, dos, tres – we were in the air! After a while we emerged from the water and laughed with incredible joy at our new found courage.
According to neuroscience, this memory contains all the ingredients for life’s dessert that makes us feel good. From an RDoC perspective, my cognitive and valence systems are all interacting to create wealth from this experience. The cognitive system enables the memory of jumping off a cliff, initially generating feelings of fear via the negative valence system, which are now almost immediately counteracted by feelings of reward via the positive valence system.
What was once a scary moment is now a triumphant memory with my mother. It’s the only thing we remember when we literally took a leap of faith, so we cherish that memory as an example of what our brains can accomplish together. These little moments of life, neatly packaged into a million memories that we hold on to, make up the good things in life.
Based on “How to Change Memories: One Neuroscientist’s Quest to Change the Past.” Copyright © 2025 by Steve Ramirez. Reprinted with permission of Princeton University Press.
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