Science Friday
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Neuroscientists are manipulating memories in mice in an effort to develop treatments for brain disorders.
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Hi, it's Ira Flatow and you're listening to Science Friday.
Today on the show, the malleability of memory.
You can't step in the same river twice. I think it's the same thing with memory, that you can't exactly recall the exact same memory twice.
Our memories make us who we are. Just ask Barbra Streisand. But seriously, despite the lyrics to popular music, memories are not frozen in time. When we recall memories, details shift in shape over time. In fact, the latest neuroscientific research shows that we can go even a step further to actually manipulate our memories and even implant false ones. I know this sounds somewhat sinister, not to mention the plot of a few science fiction movies. My next guest is optimistic that memory manipulation can revolutionize how we treat brain disorders. Dr. Steve Ramirez is author of the new book, How to Change a Memory, an associate professor of psychology and brain sciences at Boston
University in Boston, Massachusetts. Welcome to Science Friday.
Thank you so much. It's awesome to be back.
Nice to have you back. You know, I think that a lot of us think of our memories as constant, a file we can go back to, retrieve it exactly as it was stored. But that's not what happens, is it?
Yeah, we tend to think of memories nowadays as a kind of reconstruction of the past. And some research even goes far to say that we think of memories as the brain's best prediction of what actually happened in the past, which is all to say that it's a, it's more like of a silly putty dynamic process that happens in between our ears. And it's less like a iPhone video of the past.
Why is that? Every time we pull it out and put it back, we change something about it?
There's a lot of theories out there as to why memories are more malleable than expected. One that I'm particularly fond of is that We think of the ability to use memories as kinds of building blocks that can be combined and recombined as the brain's way of also enabling our ability to imagine ourselves in the future by combining and recombining parts of our past and make some prediction of what tomorrow might look like. And this is far from proven, but there's a lot of research from the past couple of decades, actually, and in humans in particular, showing that a lot of the areas of the brain that light up when we recall the past happen to also light up when we imagine ourselves in the future. So it's an interesting theory
that memory and imagination might actually be more intimately biologically intertwined than previously expected.
Do we know where memories are actually stored in our brains?
It's funny, it's funny you ask, because I think that that's the kind of question that you ask 100 different neuroscientists and you might get 100 slightly nuanced answers compared to each other. Because I think of memory as a thing that the brain as a whole does. There's a scene in Eternal Sunshine of the Spotless Mind where Jim Carrey's character is having some of his memories erased and they go in as if they were playing a video game essentially, and erasing memories by finding that point in the brain where the memory exists. And they delete that point in the brain. And we don't think of memories like that anymore. We, we think of it more as an organic, three-dimensional web of activity
that recruits your brain, high and low, left and right, deep and superficial and so on. So I think of it this way, where we've certainly narrowed down that memories exist within a brain and the certain cells and circuits and systems in the brain that make memories possible. But we don't yet know the exact point or locus in the brain, because it's more of a three-dimensional web of activity rather than a single point in the brain.
If we don't know where, do we know exactly how? I mean, what changes in our neurons to store a memory?
It's amazing because since I even got into neuroscience almost two decades ago, the amount that we've learned about what happens in the brain when you form a memory is really transformational because no matter what level of analysis you choose, you see something that happens when a memory is formed and when a memory is recalled for that matter. So if you look at DNA, for example, you get different snippets of DNA that are upregulated, sometimes even cut and edited and so on, that enables memories to be stored in the brain. If you look at individual brain cells, you see the anatomical structure of brain cells very much changes in response to learning something or memorizing something. And then if you start looking at what we call populations of cells,
so on the order of dozens to hundreds to thousands of brain cells, they suddenly start coordinating their activity with each other, almost like a symphony, to enable certain aspects of learning and memory. And then finally, when you start looking at entire different brain regions that are interacting with each other, you start seeing things like rhythms that begin emerging as well.
When we think about our fondest memories, the ones we come back to again and again, I think we assume that these are our clearest memories, the closest versions of what actually happened. How do our memories change over time?
I think they transform a lot more than we give them credit for. If I'm remembering correctly, there's a handful of studies from Elizabeth Lopstis's lab that suggest that even if we really believe that the memory that we're recalling is bona fide true, it's a part of our childhood, it's something that we remember in high-definition detail.
Right, I remember my bicycle when I was five. That was there, right?
Like, our confidence doesn't necessarily correlate with the accuracy of that memory. And I think that that speaks to just how much memories are intertwined with our own sense of self and identity and so on. There's an aphorism of you can't step in the same river twice. I think it's the same thing with memory, that you can't exactly recall the exact same memory twice. A lot of the details might stay the same, especially if it's a memory that we hold near and dear to us. But there's different parts that I think begin shape-shifting without our conscious awareness, different hues and colors, all the way to emotional textures that paint in that memory, so to speak.
I want to talk a bit about how to change memories on purpose. Tell me about the latest science. What kind of memory manipulation is actually possible? I mean, we're not talking about inception-like capabilities, right?
Right, well, it depends if you're a mouse or a fly or a human in this case. To start with the mice work, because it's the kind of work that my lab does. It is inception and it is severance. And that's the amazing thing is that there, there's so much that we can do in 2025 in rodent research that I like to think is a blueprint for what we can do in humans, hopefully soon, in a way that can be used to restore health in the brain. So for example, my last project in grad school that I talk about in the book was a project where the goal was to artificially activate positive memories. And we were able to do that. We were able to artificially turn on a positive memory in the rodent brain.
And now, knowing that we could do that, could we turn on positive memories in mice that we think show symptoms that are similar to what depression and anxiety look like in humans? Because if we can do that, suddenly, positive memories aren't just this cognitive thing that the brain does, but they can be thought of as an antidote, like a drug, that we could actually modulate or administer in a way that can restore health back to the rodent in this case, or the individual in the future. Now, that's the kind of work that I think really sets the framework now for, because in that last project, we were able to successfully reverse symptoms associated with depression, and even permanently so, by repeatedly activating positive memories in rodents.
So of course, the goal now is to scale that up to humans and ask, given what we learned in rodents, what does that tell us about what this would look like in humans as well?
I have to ask you how you're able to make these mice form positive memories? And, and how do you know that they have done that?
Yeah, it's a good question, because mice, right? They can't self-report back whether something is good or bad.
Right.
Let's say you're, you're training your dog at home. There are certain things that you know that they are biologically adapted to.
Gravitate towards, right? We know that if an animal is hungry, they will eat food. There's a lot of animals, rodents included, that are social. So socializing also is a positive experience. And there was actually a combination of condensed milk or Nutella that was the positive stimulus that rodents would almost even fight each other over because of how much they wanted to consume more of it. So that was our behavioral readout, that that was a positive experience for them because they would go back to it and seek it out again and again.
Were you able to actually see changes in the brain of these mice? That that their attitudes were changed?
Yeah, we were able to see that within the brain. For instance, the area that we were focused on is an evolutionarily conserved area that mice have and humans have called the hippocampus. So what we saw in the hippocampus of these animals was that there was about 6% of cells that would light up when the animal was forming this positive memory. And it was those 6% of cells that we were able to artificially jumpstart to activate that positive memory. And the really cool thing is artificially activating a positive memory also activated that reward circuitry and got the animal to go on and show us the behavioral responses that were indicative of recalling that positive memory.
After the break, how tapping into your memories could be a therapeutic tool.
In just a few seconds, by recalling the best or the worst day of your life, you can alter your entire biology just by sitting with that memory.
Support for Science Friday comes from the Heising Simons Foundation. Unlocking knowledge, opportunity, and possibilities. More at hsfoundation.org.
I mean, of course, I'm going to ask, since we humans, as you say, we have hippocampuses or hippocampi, whatever you call them, could you not make that happen in people, too?
Totally. And the best part is, we don't really have to do any artificial mumbo jumbo of sticking optic fibers and lasers in the brain and so on and so forth. I could just ask you, like, hey, what's a really fond memory that you have that makes you just moved a bit, maybe even a little bit euphoric, if it's a particular positive memory? And within a few seconds, your mood is increased, your cognitive flexibility goes up, your heart rate might flutter a little bit, a lot of the reward circuitry of your brain lights up. Or I can ask you about maybe one of the harder days of your life, and then suddenly, your heart rate spikes a bit, your blood stress levels spike a little bit. That happens in a few seconds. So, all that's to say that, in just a few seconds, by recalling
the best or the worst day of your life, you can alter your entire biology, just by sitting with that memory. And I think that there's something really powerful, if not untapped in that, that we can use for therapeutic purposes, or just to enable our well-being. Like, the first thing that comes to mind is something like gratitude journaling, that we know is so unbelievably beneficial for our psychological health. And gratitude journaling requires a few minutes of sitting with a positive experience that you once had, and really intentionally sitting with it. And I think that there's some real biological magic that that can do to the brain, and to our psychology, and to our bodies, even. So that's exactly the kind of work that we're hoping to discover more about, by at least trying to look at how positive memories work, at that cellular level detail in rodents.
Right. Is it possible to go even further, and use this therapy to remove bad memories? I'm thinking like PTSD, where traumatic memories won't go away.
It is, and I like to think of it as something that we can nuance as much as necessary. So, for example, with PTSD, there's a high percentage of people that, I think it was about seventy, eighty percent of people, that wouldn't actually want to erase the entirety of an experience from their past because of how much it's sculpted who they are today. We can say, can we go in and try to turn the volume down on the debilitating emotional components of that memory without necessarily getting rid of the what or the where or the when of what happened? There's a lot that I think that the past decades of neuroscience have really pinpointed to this idea that we can do that.
And then whether it's through a particular cognitive behavioral therapy, or whether it's through drug-based therapy, or a combination of both, that it's possible to, to turn the volume down on the emotional components, but while still keeping the memory of what happened relatively intact.
Your book is not only about science, your book is part memoir. What made you decide to delve into your own memories?
Yeah, that, that was probably the hardest but most rewarding aspect of deciding to write a book. And I grew up reading a lot of science nonfiction, and I felt like one of the things that I was always missing was half of the story, which was maybe the more human story behind the discoveries that I was reading about, what it's like being a person doing science. My time in the book chronicles mainly my five years in grad school with my late partner Shu Lu, and it goes through the very, the very human story of our, of our friendship together, working together in the lab to make some of these discoveries possible, and then what the implications of those discoveries are and so on.
I want to explore that a little bit more because you write about the sudden passing of your lab partner, Shu. How, how did that experience affect how you understood memory?
That process affected how I understood memory in so many stages and I'm convinced that I I'm not done growing from it. So, for example, when I found out that Shu had passed, it was it was devastating. It was the kind of thing that it really just rocks your world and puts everything on pause. So my first appreciation there for memory was kind of terrifying because I I really saw up close and personal the brutal reality that we're all gonna become memories one day. Like, that's that's the sort of the price that we pay for the beautiful thing that it is to have a life. And over time, as I began to grow my life and really accept that grief, for example, is just something
that never goes away, but something that your life really builds around. And even in this case, how I can still channel really moving memories that I have of my friendship with Shu that are providential now. So nowadays, I think of my relationship with memory, then those memories in particular, as one that's filled with a deep respect for what memory actually is and can be.
You know, I recently lost a friend who I'd known for many decades.
I'm sorry.
And and despite all of the years that we had worked together, I remember most the last thing she said to me. You know, it was almost as important as all the other years. Is that unusual?
I don't think it's unusual. And maybe we're we're two peas in a pod here because the example that I recently began thinking about a lot was the last words that Shu said to me as well. And I think it's because the first even few years since he passed, I couldn't look at our text messages. I couldn't even really begin to imagine our conversations together because it was just a brutal reminder of what once was and what can't be anymore in the future. And over time, the last words that he said to me became so crystal clear as a guiding force for just who I am as a person and who we were together in our friendship. We were invited to give a talk at the NIH for our work on memory together, right before
he passed. And I sent him a text being like, dude, we got an invitation to the NIH to give a talk. This is amazing. And his last text to me was just, that's great. Let's do this together. And that let's do this together part is almost like a guiding force now for how I just think we can overcome anything as a people.
Well, I have one, one more question for you. Where do you see the cutting edge here in researching memory? Where do you see the field going in the next decade?
The hope, at least for mice, is that one day we'll be able to have a kind of Google Maps for memory where you can pick any memory and then pause it and then zoom in and say, what are the cells that were involved in this particular positive memory? What makes those cells special? And the beauty of that is if those memories, for instance, are the ones that end up going away due to neurodegeneration or Alzheimer's, because we know the physical makeup of those cells, then this can be something that we develop, either drugs or any kind of therapeutic approach to access those cells and to try to jumpstart them again to try to restore that memory. So that I think is actually something that we'll see in the next decade or less.
I think that's something that I'm going to be mad at my colleagues if we don't have the answers to that in the next decade.
Fascinating stuff, Steve. Great book. Thank you for taking time to be with us today.
Thank you so much. This was awesome. I really appreciate it.
You're welcome. And there's a lot more by Steve Ramirez in his book, How to Change a Memory. Steve is Associate Professor of Psychology and Brain Sciences at Boston University in Boston, Massachusetts.
Hey, thanks for listening. If you have a comment or question or a story idea, our listener line, it's always open. Call 8774-CY-FRY, 877, the number four, CY-FRY. This episode was produced by Soshana Buxbaum. Lots of folks helped make this show happen this week, including
Jordan Smudjic.
Emma Gomez. Valissa Mears. Sandy Roberts.
I'm Ira Flatow. Thanks for listening.
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