← Mindset Neuroscience Podcast
Mindset Neuroscience Podcast
Our Body Keeps the Score, Our Cells ‘Remember’ with Dr. Nikolay Kukushkin
01:06:46
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- [00:10]
A
Many of you have heard of the book the Body Keeps the Score by Bessel van der Kolk. The main idea of the book is that memory is not just something contained in the brain, but that the actual cells and tissues of our body store our past experiences. And this can often affect our current life in ways that we may not necessarily understand or be conscious of. Nico's work is bringing a new understanding and validation to this idea on a cellular and molecular level. This interview has a lot of sections that will be very technical for many of you where Nico talks about some of the methods and the intricacies of cellular functioning and what he and his teams do in their research. What Nico and I have in common is that we believe that understanding things from a very zoomed in, sometimes even technical perspective, cellular signaling, and in my case it happens to be more about cells inside the brain and how that activity translates into brainwaves. Whereas Nico is looking at cells across species and cells in many different organs in the body. What we both believe is that having some perspectives that look under the hood in that sense and look within the organism can be helpful for us to understand where some of the other ideas that we have about zoomed out perspectives, behavior and psychology, human development, where all of these come from. So although there is some technical information in this episode, there's no need to memorize or consolidate or recite any of the very technical aspects of this research. However, I think that hearing some of these more nuanced and very microscopic or zoomed in perspectives can give us a sense of grounding and validation when we hear book titles like the Body Keeps a Score rather than just reciting a book title or key points of that book. What we'll see in this interview and from some of the quotes I share about his writing, we're currently in a new frontier of truly understanding what something like the body keeps score could actually mean from a cellular biological level. One of the main ideas here is that cells have memory and that the idea of memory is not just what we think on a human and psychological level, such as remembering someone's birthday, or remembering how to ride a bike, or remembering a past event. Nico's research shows us that memory formation is energetically expensive. And when we look at memory from a biological perspective, we see that memory is not just about storing more information for longer, but selectively retaining the most relevant information. As Nico states in one of his articles, when we think about memory, we often assume that a superior memory means remembering more things for a longer time. That's how we Think of computer memory too. The more the better. But biologically speaking, memory did not evolve simply to store information. It selects what information to store and what to discard. A form of pattern recognition. So superior memory means not just more information successfully stored, but the most relevant information successfully selected. He goes on to say that especially with humans, where we have so much going through our brains at any given moment, remembering everything would not only be too expensive, it would be useless. This has a practical application for us to think about. For example, in many situations, the learning we usually attempt, like trying to cram an entire textbook right before an exam. Nico states that this is unnatural. The brain's goal is to pick out a salient pattern, and the textbook is not what it considers salient or relevant. Instead, he recommends that a helpful way to improve and look at memory is. Is to listen to yourself. Use things like curiosity, inspiration, and even boredom as tools that can guide you when you feel inspired, for one thing, potentially drop other things and move into that inspiration. And he also suggests to not forget to take breaks, because we need time to digest new information. And this leads to another major theme that emerges from his work. That timing and spacing matter. How events and stimuli are spaced out in time and how often they occur, have a very deep influence on what becomes stored as information within the cells of our body. In the interview, we go more in depth into what this means in terms of hormones, insulin, and other chemical kind of processes, such as drug therapies and cancer treatment. And how he reflects this on a bigger human behavior level comes also from his writing. For example, going back to the idea of cramming for an exam. What Nico's research explores is that some concepts that we already know about how to really optimize and maximize learning and memory from a human behavior perspective is also true on a cellular level. In terms of learning. For example, we remember things a lot better when we learn them repeatedly over multiple sessions. And, and also when we space information apart, particularly in increasingly longer intervals. This is called spaced retrieval or spacing. We could take the total amount of learning and keep it the same, but if we try to cram it all into one session, our ability to recall it will be vastly diminished compared to using the same amount of time to study, but spacing that training apart. Computers don't work like that. But what we're seeing from Nico's research is that biological organisms do. In another article from Nico, he writes, the property of memory, called the spacing effect, turns out to be built into the very fabric of our body. Even Kidney cells learn better and create more lasting memories from spaced repetition. This idea of patterns and rhythms, spacing and timing. And how humans remember and learn things better. And how this relates to what cells inside the body are doing, Relates to a third theme that emerges from Nico's research. And this is that some people might feel a sense of loss or tension. When they're presented with this type of cellular and molecular kind of information. They might feel as though there's less mystery or miracle in life. That if everything is just atoms and molecules and cells. And these are all in common with many things within the universe, what makes humans special? But what we talk about in the interview and in his book Is that we see that although as we learn about life in a more microscopic, molecular way, Although this could lead to some sense of loss or tension or less mystery and meaning, what we also know that is very true to our experience Is that each of us experience life in powerful and personal ways. And we have an intuition that our experience is different than someone else's. If it's all just molecules and atoms, how can this really be? And what makes life so special? These are beautiful questions for us to wonder and contemplate with open minds. Not necessarily with the attempt to have concrete answers, but to enjoy the experience of even being able to ask questions like this. This is part of what Nico means by being a molecular philosopher. We can explore our experience in new ways. When we dive into really deep perspectives that are microscopic, molecular, atomic. And we can float back up to a different dimension or realm of contemplation. And these can coexist and can make us have deeper and more complex understanding about things, about human life and behavior. On the one hand, there are many things that unite us all. And that unite us with everything in the universe. And on the other hand, particularly with the idea of how much complexity there is. In the timing and spacing of how different stimuli occur in our environments and on cellular levels. That all of us truly do have a unique experience. And those unique personal experiences are things that we can hold in mind. As we try to understand and interact with other humans, While also holding in mind that there are many things we share with everything else in this world and in our universe. As we move into the interview and as you hear some sections that have some technical, scientific terms in them, These are all ideas that you can hold in mind. Hearing from a scientist who is diving deeply into the actual cells of her kidneys and of slugs and different organisms. This deep type of study of signaling and interaction between cells and the environment have a ripple effect in how we understand and also optimize our experience. I hope you enjoy this podcast. And I now present Dr. Nikolay Kukushkin.
- [09:28]
B
Thank you, Nikolay, for joining me for the podcast.
- [09:30]
C
Thanks, Stephanie. It's nice to be here.
- [09:32]
B
Thank you. So we're going to dive into the absolutely fascinating research that you are a part of and you were leading. But first, I would love to hear more about your story and just how you got to be where you are today.
- [09:48]
C
Sure. So I was born in Russia, or as I sometimes say, I was born in a city and country that don't exist anymore, in Leningrad, ussr. So I'm part of ancient history. And I tell my students I'm from USSR, they think it's something around World War I, maybe, you know, they get pretty shocked. Yeah. So I went to college in Russia, but I should probably start by saying I had a kind of a crazy childhood in the 90s in Russia. I traveled a lot with my parents. I really grew up not so much in Russia as much as everywhere. Mostly around Europe, different places in Europe, but we also spent time in Japan. So I already had a cosmopolitan childhood. Sweden, Spain, Portugal, Italy, Austria. I think that that's. Those are probably at least the big ones, but we traveled a lot, so, you know, I got to see a lot, and I think that that's the single most important thing that happened in my childhood.
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B
So you got to see a lot of different cultures and contrasts.
- [10:51]
C
Yeah, yeah, yeah, yeah. And part of it is that I no longer really have a. I've never really had an attachment to a particular place. So, you know, some people would say that's a bad thing, but, you know, I've never seen. Seen it that way. Yeah. So I went to college in Russia. I left after college. I went to the UK. I did my PhD at Oxford, which was amazing. I love England and Terry Butters was my advisor. Really grateful for the experience. It was a wonderful time. And I met my wife in Oxford too, so that was a big deal. Yeah. And then we moved to the US and we've been here for. Moved in 2012. So it's like 13 years now. I lived in Boston for a while, then moved to New York and I joined Tom Carew's lab here at nyu. He is a pioneer in long term memory research and everything I know about the brain I've learned from him. So I've been with Tom for these 10 years, sort of graduating from a postdoc to more of a senior scientist in the lab. But at the Same time, I also have a teaching job here at liberal studies. That's where I am right now. So I am a clinical associate professor here. And that's my. My main job at the moment. But, you know, I combine research and teaching.
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B
So many different, I think, threads that you probably saw about humans and human behavior growing up in that way. What drew you to neuroscience in the first place?
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C
Well, it wasn't the first thing that drew me. I am a cell biologist at heart or molecular biologist. That's really what I understand. I think that my intuition is for cells. That's where I can feel what they want, how they operate. And neuroscience was secondary for me. I came to neuroscience. I like to say that I came to it from the bottom up. Most people come from, you know, from psychology, from sort of bigger things to how they work. For me, it was more. I was interested in how molecules talk to each other and how cells operate. And then from there I was like, okay, what can we build out of this? Can we build a memory? Can we build a mind? So that's sort of the approach with which I entered it. So I came to Tom's lab as a, you know, straight up cell biologist, total novice to anything neuronal. You know, read Kendall's neuroscience textbook before I starting the lab. That was my introduction, but it was very organic because Tom's lab was already very much in between traditional neuroscience and cell biology. That's what Tom's wheelhouse has always been. So that's why I went to his lab, because it seemed like that's the nearest that you could. The shortest path that you can take from molecules to a brain is through a sea slug. And that's what Tom's research model is. So that's why I joined his lab in the first place.
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A
Wow. Very cool.
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B
In terms of molecular biology. And before you kind of entered the neuroscience aspect, was there anything that really stands out to you that surprised you or maybe didn't surprise you about cells in general?
- [14:28]
C
Anything that comes up, Those are endlessly fascinating. You know, honestly, to this day, even though, well, I like to think that I understand neuroscience now and I read both, but if I had to compare how many times I read a paper and I go, wow, I did not expect that. Cell biology, you know, neuroscience, by and large, of course, sometimes it blows your mind, but mostly it's like, okay, okay, we're confirming something that I already sort of thought was happening. It's great. That's great. We're doing this in a more sophisticated way. We're understanding a Little bit better. But it rarely gives me this mind blowing, you know, this totally changes the way how life works in my mind. You know, and with cell biology, it happens all the time.
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A
Amazing.
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C
I know you asked about what surprised me earlier, but just this morning I was reading about obelisks. That's something that I only became aware of just a few months ago. Apparently these, these structures that are neither viruses nor mitochondria nor bacteria that apparently have some DNA and they, there's trillions of them in our bodies and our bacteria. Nobody knows what to make of them, where they come from, what they do. You know, that kind of thing can happen. It's much harder for that to happen and you know, in, in larger things. So before I came to neuroscience, so my PhD was about protein degradation, quality control, how proteins are processed and how they get discarded if something's wrong with them. And that's a, it's a great example of the sophisticated information processing in a cell. What I studied specifically, there's these glycoproteins that receive a carbohydrate tag when they get first produced. So protein synthesized that receives this very specific molecule that gets attached to it. Just these branches of sugars in all directions, very specific. And then as it gets processed through steps of maturation in the cell, it gets grabbed by different enzymes that do something to it. And as they do it, they also trim a little bit of that carbohydrate and that serves as a tag for the next enzyme to then grab it and do the next step. And so they communicate with each other through this carbohydrate, which is insane to me. So that's what I did my PhD on. I think I can see now in hindsight from there how, from there I go to. How do we get to memory, right.
- [17:06]
B
This, that, this incredible communication system. And to me, I see it in so many other realms too. Like even the plant realm. I was just hearing about flowers and the acoustic potential there is about how they're communicating or either sending signals, you know, receiving signals. Like there's these, this incredible communication that's happening on these frequency levels that we have not nearly tapped into what's going on. Yeah, right.
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C
So I don't know exactly the research that you're referring to, but that is incredible. You know. Yeah, we don't think of plants or plant cells as communicating on a. You know, it's not a surprise that there is some communication. You know, there's some signals going on between cells. You know, everybody understands hormones. But what I think is missing in the awareness of how most people think about cells is just how sophisticated this communication can be, how combinatorial, how flexible, how many different responses can one cell or, you know, one plant elicit in another one. We tend to assume that it's just, you know, switch and then that's it. But it, of course, is a lot more sophisticated.
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B
So much more sophisticated. Love it. I want to dive more into all of your research. It just makes me think of. This is from a while ago, but I remember reading that cells in the retina already are making some form of a computation before signals are even being sent. So there's that very sophisticated.
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C
Even begins in the ice.
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A
Yeah.
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B
Yes. And I just think, you know, just to pause there for my audience, who are not neuroscientists, to just reflect on this idea that there is so much going on on this cellular level within us before, in a sense or in parallel with everything that we kind of look at in terms of the brain and how sophisticated we believe that is so much within every cell of our body is. I feel like that ties into. I think it says you're a molecular philosopher, too. Can you say a little bit more about what that means?
- [19:37]
C
Yeah. So it's a. It's kind of a funny term. But what I'm trying to encapsulate on this is two extremes. That's what I like to write about. I like to think about. You know, I. It's also how my research relates to my teaching. I teach here at Liberal Studies, where this global multidisciplinary department. We like to think about things big. So I study the smallest things, but I think about them in the biggest way. So that's what molecular philosopher tries to bridge. Usually molecular biologists don't think about philosophy and philosophers don't think about molecular biology. They're just too far away from each other to read, make this connection. But I think that there are some really deep philosophical questions that are solved by looking at molecules. And that just means that they are the biggest questions. They are the core questions, the questions with which everything starts. The ideas such as memory and even life. It all boils down to small things, to molecular things, to even atoms.
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B
Right. And they exist within us.
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A
They're everywhere.
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B
Yes. It's something that ties all of us together in a very universal way.
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C
Together and us with other living organisms and us with the universe, if you want. Connects everything.
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B
Yeah, exactly. So, all right, let's go into a few. I mean, there's so many threads we could pull on here, but what Are you most excited about? What would you like to share that comes top of mind in terms of memory, you know, first and foremost?
- [21:16]
C
Well, a recent research has moved the concept of memory from the brain into the entire body. That's what we can talk about. This, this paper that came out in November was about memory in non neural cells, memory outside the brain. So what we have shown is that cells that are not neurons, that have nothing to do with being part of the brain, they have ways to memorize their experiences, to retain an imprint of what has been happening to them. And the way that they do it is exactly the same as what neurons do when they memorize their experiences. And by their experiences, we mean our experiences, our mental experiences. So what is happening in our brain as we're learning something is the same thing that is happening to a kidney cell or a skin cell, or really, you know, we believe any other cell, it's not specific to any particular organ or particular cell type. It's a cell thing. Every cell has experiences. Every cell sees patterns of neurotransmitters, if it's a brain cell, but hormones or nutrients, salts, liquids, if it's any other cell, it still sees patterns of chemicals passing through it at different times. And what our research shows is that these patterns matter, and they matter on a surprisingly short timescale. A cell such as a kidney cell can distinguish between a chemical arriving for a continuous interval of 12 minutes versus it arriving for pulses of 3 minutes separated by 10 minutes. So the difference is those 10 minutes interspersed within the long pulse of chemical exposure. You wouldn't think that a generic cell has a way to tell did something happen continuously or did it happen with these 10 minute repetitions? But that's what brains can do. Brains are very good at that. It's known as the spacing effect. Any brain, any animal, it's not the human thing. It happens in every animal. You test if you have the same amount of training that you give to an animal, if you split it into multiple intervals, you will produce a better memory than if you do it all at once. When it's cramps, that's called the spacing effect. So it's not a surprise that brains do that. But we never expected that generic cells would do that as well in such short timescales. And so what our research revealed is that they do, they do have a way of telling apart mast exposure to a particular signaling chemical that we picked to emulate what is happening in neurons versus the same exposure space and time. And that is this temporal sophistication that nobody expected. And so this is a proof of principle. We don't know exactly which cells in our body respond to which patterns of which chemicals in which ways. But what we have shown is that they have a capacity to do so on a surprisingly short timescale. And so when we're thinking about anything that we're doing on a schedule, we're eating on a schedule, we're exercising on a schedule, we're going for walks on a schedule, we're taking medicine on a schedule. Those are patterns in time. And two cells in our body, that means patterns of chemicals in time released at different times, nutrients arriving at different times, you know, your muscles releasing exerc related hormones at different times. And all of that might result in different outcomes depending on the pattern. Not necessarily faster, not necessarily slower. We don't know what the optimal pattern is. There is no theory behind, you know, what's the best pattern of exercise or what is the best pattern of nutrient consumption to maximize your health, to maximize weight loss, maybe. Or if we're talking about medicine, what is the optimal pattern of drug delivery? If you're trying to kill cancer, the idea normally is, well, you feed the person poison, that's what chemotherapy is, and you're trying to give them as much poison as they can take for as long as possible so that you kill that cancer cell. And that's why it's such a difficult treatment. But maybe there are other ways. Maybe there is a pattern that we can figure out and we don't know that, but maybe there is a pattern in time that will be more efficient than just elevating this poison in bloodstream for as long as possible. So this research opens up the possibility that these patterns and the memories that cells form, we can call them memories without quotation marks because they work in the same way as our normal memories in the brain. They use the same molecules, they process information in the same way. It's not a metaphor, it's literally the same process. And we now know that this same process in all cells in our body can have outcomes that we haven't been aware of.
- [26:30]
A
Yes. Wow. Really fascinating.
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B
So I'm hearing patterns and rhythms that they matter in a sense. So how do you, in terms of the, let's say the kidney cell, how do you know that it remembers? Is there an anticipation effect like is. Yeah. How do you know that?
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C
Yeah. So. Well, this really cuts to the heart of what, what we mean by, by memory.
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A
Yeah.
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C
You know, when what most people think about when they think of the word memory Is introspective. It's what, what you personally, subjectively imagine when you close your eyes and think about the past. But that's not what really neuroscientists study. By and large, mostly neuroscientists that use animal models, at least they study behavior. They study changes in how the animal moves around. That's really what behavior is. So what neuroscience considers to be a memory is something that happens inside of the brain that changes the behavior of the animal in the future.
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B
Right.
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C
So it might involve anticipation, but not necessarily. If an animal, for example, a skill, A skill is a memory that doesn't necessarily involve the anticipatory component, and that would still be called memory. Even though maybe we wouldn't necessarily call riding a bike memory. That's not everyday language, but it's the language of neuroscience. And why does neuroscience use this language? Well, because we know that skill formation works in very much the same way as episodic memories. That to a neuron is largely the same process, the synaptic plasticity is induced in similar ways. So we're using the same term for both of those processes. And so what our research shows is that basically you should stretch this term even further because the same process occurs beyond skills or episodic memories and affects the processes that are occurring to other cells in the body. So what does that mean for them? Well, it's not the same thing as it means for us introspectively. It doesn't have all those components of attention, anticipation, reward, binding of multiple aspects of experience. All of those are specific features of our own introspective memories. Memory of a kidney cell is much simpler. It could be something such as, you know, it saw a lot of salt and for the next two days it's pumping that salt more actively. That would be a memory. How do we see it? Well, we use a proxy for it, and we make this proxy based on what we know about neurons. We know how memories are formed with sufficient amount of detail. We know how they are formed in neurons, for example, in episodic memories during skill formation. We know what sort of molecules are activated inside neurons. We know what genes they turn on. We know what those genes then produce and how they then go on to restructure the neuron. We know those steps. So what we can do is we can artificially turn on the same molecules in our non brain cells. We don't know what turns them on and if, even if it is being turned on in the real life situation, but we can do the same thing to them as what we know is happening to neurons in the brain. And so when we do that, we can do that at different times. We can do a chemical pulse of like I described, 12 minutes or four pulses of three minutes. That's a standard protocol. So we do turn on the same molecules inside that cell as in neurons. And then we watch for the same genes to be turned on, and we watch for how long are they being turned on. And that is our proxy for these cells are doing the same thing as a neuron does. They're turning on the same genes, they're interpreting fast signals. That's what we are doing to them. And they're producing slow responses. That's what this turning on of the gene is. And we watch it. We don't want to watch it being turned on over hours. We watch it decay over multiple days. Even a few days later, we still see that it's being turned on. And how do we know it's being turned on? Well, we have this special reporter that is introduced into those cells. So genes have promoters. Promoter is a way that you turn on a gene, a dedicated transcription factor protein that turns on genes, lands on this promoter. It's part of the DNA that happens just before the gene. So it lands on this promoter and that turns on the gene that starts transcription of that gene. So we can use the promoter is like an on button for a gene. We can take that promoter and we can place just after that promoter, an artificial gene. It's actually taken from a firefly. It produces a protein that glows, produces light. So the button is the same as in all those memory genes that we are interested in. We want to know if the cell is turning on memory genes. So we place this memory gene button inside of the cell and we give it this gene that produces a glowing protein. So whenever the memory genes are turned on, this glowing protein is produced. The cell starts glowing. Basically, that's how we know that it's formed a memory or put it in a machine that reads that light and it tells us how much of that light it produces. And we watch it as light go up, up, and then slowly, slowly go down. That's our proxy for memory that the cell forms.
- [32:33]
A
Right.
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B
You know, I want to come back to just my audience, because they're not neuroscientists. It's a lot of technical language. So we're going to translate a little more for them. So to me, I'm hearing that it is so much about the behavior. Like what we're saying is that memory, the way we understand the effects in a way of memory is the behavior, the subsequent behavior. And so in this case, it can be the turning on of a gene, for example. And in humans it looks a little more complex because we got lots of different systems going at the same time. I do also want to just. There's some people that might need a refresher on episodic memory, procedural memory. So can you just say a little bit about that compared to what some people are picturing as memory?
- [33:29]
C
Yeah, so. So, you know, forgetting cells and molecules and genes and all of that. Just thinking about memory from a psychological perspective, from a personal perspective, there are a few different types of memory. The most obvious memory that we all think about, when we think about, you know, yesterday, you're imagining some situation that happened to. That's called an episodic memory. It's a memory of an episode, also called autobiographical memory. It's your autobiography stored in your head. So what is this memory? If you really start breaking it down? It's not like it's a video file of what you observed with audio and video. It's a combination of everything that you have been experiencing in a given moment, not what has been happening. It's not a snapshot. It was what, what your brain has been going through in that moment that has been captured. So that's called an episodic memory. The way that it works is that we have this special add on to the cerebral cortex. The cerebral cortex is this part of the brain that really processes everything online. It's the thinking part. You can think of it as the processor of everything that's incoming through our sense organs, then gets parsed into concepts and ideas. The cerebral cortex. There's a visual part of the cerebral cortex. There's an audio auditory part, there's a touch part, there's an abstract ideas part, language, part math part. All of those different parts, they process what's going on in a given moment. And at the same time they send a copy of whatever they're processing. They're sending a signal into this add on to the cortex called the hippocampus. The hippocampus takes all of those signals between currently active parts of the cortex and says, okay, that's a unit. We're going to bind that together. We're going to bind all those simultaneously active things. You know, the smell of the coffee, the face of the person you're sitting with, the song that's playing in the background. We're going to bind all that together. And that binding is that episodic memory. So when you're coming back to that memory, you can pull in one of those strands with a song, and that unpacks the entire combination. It reminds you of everything that's been going on. You know, the person you've been having this conversation with, what you've talked about. It all unpacks as a unit back into the cortex. So it's like the hippocampus stores patterns of the cortex and then it replace them back in the cortex. That's how the episodic memory works.
- [36:15]
B
If I want to pause there, because they'll need to digest, of course, and then I want to go into the next one. What I kind of want to pull in there is this idea, you were kind of saying too, that it's not like this one to one translation, there's not like there's the world. And then it somehow is captured as a snapshot that's universally exactly the same for everybody in that moment. It's what we are experiencing on a cell level in that moment that is also very personal to us too, because it is right and it's experience dependent because our eyes will focus on one thing versus another. Different things like that. Is there anything more you can say about that? Like how personal, in a way it is for each person on that cellular level?
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C
I think it's a nuance that a lot of people miss, because even when we think about science fiction, it's a trope that somebody comes up with some mind reading device and plug that into your brain and then your memory gets projected onto a screen and it's a video, you know, and everybody can watch it and you think, well, okay, we don't have this technology, but in the future, surely we'll be able to do that. And we already have technology to kind of get some idea of what a person currently thinking, the person's currently thinking. So it's natural to assume that, okay, it's going to get the resolution is going to keep getting better and better and better. And eventually we have a video file that you can download off your brain and everybody can watch it. But that's just not how it works. There is no video file. What is stored is your personal experience. And that experience is different for every person because it depends on everything that has been happening to you for your entire life. Your entire life shapes your brain. Every single experience that you go through modifies something in that brain. And that changes how you see things, what angles you consider, what you pay attention to, how you memorize it. And so what one person remembers is going to be completely different from another person versus memory. That doesn't mean that one memory is better or worse. They're just different angles. Memory is just fundamentally private. It's not something that you can abstract from a brain, remove from a brain, and have it as a standalone object like we have with video files. The only reason you can do it with a video file is because all computers are exactly the same. They're built through the same components. You can plug one thing into another computer and nothing will change. But that's not how brains are.
- [38:53]
B
I love that. I think that's such a beautiful point to make for people is how personal and private and it's not this video file. Because I just think too, in today's world, there are a lot of people that have such certainty about how they remember and perceive things, as though it is absolutely the way they perceive it. And yet what we understand and what you're kind of saying as well is that there. There's so many experience dependent and memory dependent experiences that are happening within us that will change how all of that is formed and captured and then replayed and all that. So yeah, yeah, there's something universal in some ways about us. And then there's so much that is very personal for each person. And I think it's helpful for us to hold that in mind too, when we are, you know, sharing things with the world and reacting to other people that they may not have the same perception and memory as us. And we can rejoice in that.
- [40:05]
C
Yes, I would say in general, it's a great thing that our memory is flexible. We do. We don't want to remember everything exactly as it is. We want to. First of all, this would be too much to remember. We need to parse information that we sift through. We need to extract the most important things and forget the irrelevant things. Otherwise it would just be too much to sift through. Essentially we would remember everything and nothing at the same time. But also there is a dark side to it because there are also things like eyewitness testimony. And as you said, people are very sure about the authenticity of their memory. If it is clear in their mind. They assume that, well, the memory is clear, so that's how it was. But it's demonstrably not the case. You can be completely sure of what happened to you and yet that would be false. It's very difficult to prove that because those kinds of changes happen over years. But there have been a few important studies like the 911 memory study. It's useful to have A reference point in such cases that you can then return to several years later to identify what memory you're talking about. So there have been a couple of studies that did that. One was immediately after 9 11. A few hundred people were interviewed about just their experience during 9 11. What were they doing, how they felt? So at first that memory was just maybe the day before, very fresh, and then they came back to it a year, year later than three years later. And basically it's not the only study that does this. And one of the invariably shows that memory degrades to a very significant extent by three years. You forget half of it, and yet it doesn't feel this way. You're completely sure this is what happened? I was sitting in the kitchen, I was watching the tv. And that could be completely false. It might be a totally different story from what actually happened. And yet in your mind it's completely clear. So, yeah, I think useful for people to realize that just because it seems like this to you doesn't make the memory wrong, but it doesn't necessarily mean that that's how things happened.
- [42:26]
A
Right, yeah. So.
- [42:28]
B
All right, so that's kind of that psychological realm that we're touching on, thinking about episodic, then just another type of memory that we could talk about.
- [42:40]
C
Yeah, the procedural. Procedural memory is another kind of memory. So. So we've talked about this episodic memory, which is a connection between simultaneous parts of experience and this. What did we just say? What did we call it? Instrumental learning? Did we call it a skill? We can call it a skill, a skill or a habit. That's also connection, but it's a connection not between these strands of experience, but it's a connection between intended action and result of that action. So, for example, when you're playing a piano, when you're learning to play the piano, first you have to direct each movement with your cortex. You have to move each finger independently. It's very tedious and it's slow. But then occasionally you play a successful tune. You've used your muscles in your fingers in a way that proved to yield a successful result. So you've achieved this result, you've played this tune correctly. And in that moment, your brain releases dopamine, this chemical that helps us store this combination of movements that just occurred. And that happens in a part of the brain called basal ganglia. So it's sort of outside the cortex. And those basal ganglia, they gradually remember which combinations of movements lead to this successful result, which ones are unsuccessful and which ones are successful. And then later, as this learning progresses, as the basal ganglia gradually learn that you can activate that combination just by thinking about the context, these intended result, what you want to achieve. This moment in the song comes up and you think about it. And then the basal gang, they just unpack the entire combination of movements. So also a connection, but between context and result versus episodic memory is a connection between simultaneous parts of experience. But it's all connections. It's all connections between neurons. And a neuron doesn't really know is it connecting results to the context, or is it connecting a vision to hearing, to a neuron? It's all just chemicals arriving at different times. And the way that they react to those chemicals by changing themselves, by turning on this gene or that gene, restructuring their synapses, those ways are the same. Regardless of whether it's an episodic memory or instrumental memory, that is the level that we are more interested in. We're interested in looking at it from the perspective of a neuron rather than from a perspective of a human to home. Those are very different things, right?
- [45:39]
B
Yes.
- [45:39]
A
Okay.
- [45:40]
B
And so then speaking going into other types of cells that are not neuronal, what does that look, look like more?
- [45:51]
C
Yeah, I mean, we. So we don't yet know exactly what that means for real life. Exactly what. What sort of things are they really reacting to? We just know that they can and they have the capacity to distinguish between fasting and a slow thing and a repeated thing and a continuous thing, those kinds of things.
- [46:07]
A
Y.
- [46:09]
C
What it might mean is whatever those cells are doing in their everyday life. Well, I can give you an example that we do know about from the digestive system. Pancreatic cells that produce the hormone insulin, they're actually really reminiscent of two neurons. In some ways. It's just like a neuron that doesn't have any dendrites or axons, that is like a ball, but it has this interface with which it releases the insulin into the bloodstream, which looks very much like a synapse. It's just like if one synapse and make it into a cell, that's what it looks like. So it releases insulin when it feels sugar. When it feels nutrients arriving in the bloodstream, it releases a pulse of insulin. And insulin helps control. Helps absorb that sugar from the bloodstream. So if you expose those pancreatic cells to a large pulse of sugar, if you just maximize the sugar as if you've taken a massive meal, well, they will release this large pulse of insulin. But then you wait 20 minutes and you do the same thing again. You once again throw a lot of sugar at them. Now they'll release that insulin, but they will release twice as much. So that is just like a neuron getting sensitized to danger. You've shocked an animal and then 20 minutes later, that neuron releases more neurotransmitters. Same thing happens to this pancreatic cell. So that's an example of what can that experience mean? And this makes a lot of sense because if you think about it, how would that apply to real life? Well, you are an animal running through a jungle and you found this massive meal of sugar and you've eaten it and your body can barely cope with absorbing that sugar. Well, you probably want to ramp up your sugar absorbing capacity so that maybe you'll find another tree and you can store all those nutrients for later. But if you had it constantly ramped up, you'd probably be constantly hungry and fatigued, and that would also not be productive. So it makes sense to adapt your body to circumstances. That's also the feature of. That's also why we need memory. Memory is about adapting to circumstances, changing yourself for the future. And so the same is true for body memory.
- [48:28]
A
Memory, yes. Okay.
- [48:29]
B
Oh, that's really interesting. So, and it, it just makes me think like going back to a meta view, you know, cellular to meta view of how much our. What we get exposed to, how it changes our, you know, our future behaviors, obviously. But that, that's important for us to keep in mind too, that if we have unhealthy or kind of maladaptive things that we are constantly exposed to, there's going to be what's considered in quotes, adaptive in some way response, but it's to the maladaptive or unhealthy exposure. And then it kind of. Would you say too, based on the research you've seen, that sometimes that maladaptive, I mean, we're going to call it an adaptive response to too much exposure of something that, that can then become the default response, regardless of what is being exposed to.
- [49:27]
C
I think it's possible. I don't know enough to say that about any part of a healthy organism. At least what I can say that this can be true for cancer cells. If we consider drug resistance a form of memory. And there are labs that do that. It's not our specialty. We haven't really touched drug resistance in our paradigms. But there are people or lab, for example, who are interested in cellular memory in the context of how does a cancer cell adapt to drug treatment to become more resistant to it. And in that case, for sure, that kind of memory becomes the new normal. It's stored in the epigenetic state of the cell. What that means is that the cell basically marks up its genes into use this gene more, use this gene less. And that information, it's not the genes themselves, it's how you use those genes. But that information gets passed on as the cancer cells divide. And so their daughter cells also retain those tags that tell them how to best use those genes to stay drug resistant. So that form of memory can become a new normal. And of course, we want to, you know, undo that, and we want to make the cell forget that, that state and that new normal and revert back to a naive state.
- [50:57]
B
It still, it highlights just how much sophistication is happening, you know, and how incredible this communication system is, you know, this tagging almost and passing on to future generations. And so I just think that's really profound for people to think about, you know, also just in terms of, of what we are ingesting and the rhythms and all of that, that there's so much communication happening without our awareness, that.
- [51:24]
C
And so much that we don't know, so much that we still are yet to find out. Because almost everything we know about, say, you know, what does this drug do to our body? Or what does this food do to our body? Almost everything we know is just like, what if you place just that thing into your body for hours or days, Just that alone, or if put it onto cells and just let them sit like that. But what our research reveals is that there's this time layer to it that just opens an entire new dimension of complexity. We're thinking of it in static terms, but how those things interact with each other in time matters. And when you start adding that dimension, when you realize that we were so far from being able to, for example, emulate a living cell using artificial intelligence. There's a lot of talk about that right now. It seems that we're almost on the verge of, you know, machines being able to simulate complete living organism. No, we're very far from that. I mean, I've given up my intuition as to how fast artificial intelligence progresses. So that might mean another year, who knows? But at this point, but at this point, you know, we just still need so much wet data. That's what we call it, you know, a real life pipetting real cells that you're asking questions before. You can model that on a computer. We just really don't. It's a black box. We really don't know how cells react to these patterns in time. We've just realized that they do.
- [52:57]
A
Wow.
- [52:57]
B
Yeah. That's really also very powerful to be thinking about too, in terms of everything we know about human behavior and how we study it.
- [53:05]
A
Because.
- [53:05]
B
Because we're not adding that time dimension to it.
- [53:09]
C
100.
- [53:10]
B
And you know, even if we were to keep extending that timeline and trying, it still wouldn't replicate life in that way, you know, because we're not going from the origin to the end of the timeline.
- [53:22]
C
Yeah, definitely. I mean, genetics store that imprint of those billions, billions of years into the past. But there's more than genetics. There's. There's more experiences that are preserved. Preserved on different timelines, like epigenetics that I mentioned. It can preserve multiple generations. Not maybe all of the generations that go to the origin of life, that's our genome, but it can preserve experiences of multiple generations. And that can continue affecting potentially every cell of our body. We know very little about that. I think it's the timing that maybe this is the biggest unresolved dimension of biology in general. Because it's so hard to work with. It's very hard to do. To study these sequences and patterns of inputs, not just a single input or a couple of inputs. Wow.
- [54:16]
A
Yes.
- [54:17]
B
So as we wrap up, I would love to hear if you have anything, first of all, anything else that you would love people to know about that you're excited about, and also anything related to the sea slug that you mentioned earlier. Yeah. What would you love to share?
- [54:36]
C
I would love to share that I have a book coming out October. It will not just be about my work, although it will be in part. And sea slugs will be there for sure. Prominent part of the book. But in general, the book is called One Hand Clapping, Unraveling the Mystery of the Human Mind. What the book is about is this tension that I think we all have and sometimes on different levels. But a student came in and asked me the other week if. If we're all animals. So science tells us if we're all animals and there's no meaning or anything like that, then why does it feel so different to be myself? And I think there are many layers to this question. It feels different to be a conscious first person experience, as opposed to me looking at you or me looking at any other person. My person is different from all those other third persons. Being a human seems very different from being any other species. You know, we're the only ones that send the rockets into space. And yet science tells us that we're all kind of the same. And there's no, like, sharp lion. And chemically we're just like a plant and we're 98% the chimp. So what, what makes the stark difference? The same is true for life versus non life. Being alive seems like a miracle, but then is it all just atoms and molecules? So that's what the book is about. How do you resolve this tension between everything being the same and between me being this very special thing on so many levels? And so the book goes from the origin of life from the very beginning, and traces this, what I call essences, these ideas of nature. What did nature intend by a living organism? What did intent by an animal, a primate, a human, a conscious individual. That's what it is about.
- [56:51]
A
Very cool.
- [56:54]
B
Oh, what's the significance of the title, One Hand Clapping.
- [56:58]
C
One Hand Clapping. It refers to a Zen koan which asks us to ponder the imponderable, the sound of only one hand clapping. And so in the same sense, I ask in the book unanswerable question of how can a conscious, thinking individual exist in this dull world of atoms and molecules? And what I find, what I argue for in this book is that this first person experience, the very experience of being alive, it evolved as part of the natural world, is not opposed to it, but it is an organic part of the journey from the origin of life to the present day.
- [57:49]
A
So cool. Yes.
- [57:51]
B
So, and then you were going to talk about the sea slug.
- [57:54]
C
Yeah, a big part of the book, because that's really where my understanding of the connection between molecules and the mind comes from it, for me, that they are this bridge between simple things and complex things. Because when you start looking at the world from a perspective of a sea slug, you realize that all of those complicated things that we think are somehow separating us from, you know, material reality, that make us somehow some other form of existence, they are ephemeral. They are just there because we're so complex. And if you simplify, as sea slug is simplified, you realize that all those parts are there. Like, for example, thinking, memorizing, abstraction, deriving, you know, abstract entities from specific experiences. It's all there. It's just something that's happening to a couple of cells and maybe a few molecules. And you can understand all these complicated things through really simple patterns of very abstract things. That's what sea slugs, I think, give you. They. They give you this. They give you a way to strip away the layers to reveal the original design, to see what the intention of nature is behind the brain, behind memory, behind Thinking behind experience. And for that, I think they are fantastic. I love them very much.
- [59:30]
B
That's very cool. I love it. And as you speak of the Zen.
- [59:34]
A
Cohen.
- [59:37]
B
I studied in some monasteries many years ago, and it was under the mentorship of an NYU professor that's still there today, Zoran Joseph. And to me, I feel like something that is coming out from what you are talking about is the essence of things. And that we, you know, we are so quick to try to label and categorize. And there is this experience of life that is deeper than all of those ways. We're trying to categorize everything. And in a sense, that the simplicity of the sea slug, you know, I feel like, has reflections of that, that there's this experience we're having. It's on a cellular level, and there's something very simple about it in a way. But we do use a lot of words and labels that get us to, in a way, narrow our awareness or narrow our experience because we want to, you know, categorize it in some way. And there's.
- [60:36]
A
There's a different.
- [60:37]
B
There's a different way. We can also experience life in a more open way. I love, too, just the different threads of tying such simplicity to us as well, that when we look at things on this cellular level, we're seeing communication, we're seeing sophistication and complexity and that, you know, just keeps expanding out in. In different ways. But it's.
- [61:11]
A
It's all there.
- [61:12]
B
It's in on the tiniest, tiniest, tiniest level.
- [61:15]
A
That complexity is there.
- [61:16]
B
And I just think that's just so beautiful and fascinating to think about.
- [61:21]
C
And it's not just. It's not just words. It's not that we. It's not that we just use the same word to describe simple things as we use to describe our complicated things in nature. You know, we always think about. About the evolutionary origins. Things grow out of other things. And so our complicated thing has literally grown out of that simple thing. It's not just the metaphorical connection. It is a literal. Literal lineage leading from simple things to. To our minds.
- [61:49]
B
Yeah. And it's cool to even reflect on in a way what nature's intention was for such complicated and complex kind of thinking. Thinking that we may be very much on route to something that we don't even understand. Exactly.
- [62:06]
A
Yeah. Yeah.
- [62:07]
B
Beautiful.
- [62:09]
A
Yeah.
- [62:09]
B
Were you gonna say something else?
- [62:11]
C
Oh, yeah. And I was just gonna say that's another thing that. That my book considers. What, what, what is. Did our evolution stall? Right? Are we gonna become flying humans or is there gonna be something else that will, will.
- [62:27]
B
Will shift, right?
- [62:29]
A
Yes. Oh, I love it.
- [62:31]
B
I'm a big science fiction fan too, so I feel like. Yeah, this all ties in. Well, thank you so much for beautiful, thoughtful interview. Where can people find out more about.
- [62:44]
A
Your book and your work?
- [62:46]
C
Yeah, everybody's welcome on my website nikolaikukushkin.com or following me on social media. I'm on Twitter nikokushkin, but all my links are@nikolaikakushkin.com Great.
- [63:00]
A
I'll put those up on the website.
- [63:02]
B
As well so they can find you.
- [63:04]
C
Perfect.
- [63:04]
B
Well, yeah, thank you so much. It was lovely to speak with you.
- [63:08]
C
Thanks Stephanie. This is wonderful.
- [63:18]
A
Thank you for joining me for that podcast. You can find out more about Nico at nikolaikokushk. N I K dash O L A Y K U K U S h k I n.com he has wonderful blog articles on that website, including Are humans running out of Memory? White Bear Memory Erasure? Is it possible to get rid of a memory you don't want? What food comas and sea slugs teach us about memory and why cramming doesn't work work and what's going on in the minds of babies. He has a great depth and breadth of knowledge and how he connects ideas together. So I hope you check out his work. As always, you can learn more and get all the references and resources from the Mindset neuroscience podcast@stephaniefay.com I have a lot of things behind the scenes going on in the works for the summer and having an incredible time with with the participants of my 2025 NeuroLeader Academy. Some of the insights and future presentations that they are planning to present at what we call our graduation showcase in September are absolutely phenomenal. There is a lot of depth and complexity that these coaches and leaders and marketing executives, district superintendents, people working in mindfulness and holistic spaces, a whole great variety of people coming together. They are helping take complexity but simplifying it for their specific clients and audiences. And that's really the goal of the neuroleader Academy. I am so excited and honored to be running this program. I only run it once a year, so it did sell out this year and does sell out every year.
- [65:13]
C
Year.
- [65:13]
A
I will be holding it again next March, but in the meantime you can check out stephaniefay.com and I will soon be posting a profile of all of the people who are participating in the program so you can get a look at their work and how professionals and coaches, leaders and teachers are translating and learning about neuroscience in very embodied, socially oriented ways and how they are applying this to their work as well as many of them getting brain maps and we are looking at how their brainwave profiles relate to what they are experiencing in life so that eventually they may even be able to offer this to their clients. So just take a look at that. There's also a more specific page, stephaniefay.com neuro-leader-academy and there will be more about this in the new year. There are also plenty of blog articles on my website that you can check out. In the meantime, thank you again for all of your support. As always I appreciate a five star review and for you to subscribe if possible to this podcast. It helps me continue to spread the word and share more and more of this information with bigger audiences. I appreciate all of you listening all the way to the end of this podcast and I will catch you in the next episode.
- [66:37]
C
Episode.