The video explores the intricate pathways in the brain related to memory creation, consolidation, and retrieval, posing essential questions about the impact of emotions and the potential for scientific manipulation of memories. Neuroscientist Dr. Christina Alberini from New York University provides insights into how memories are organized, categorized, and differ in their form and function.

Discussions in the video address diverse memory types—short-term versus long-term and implicit versus explicit systems—crucial for understanding how memories influence behavior and survival. Additionally, it considers the evolution of memory research from simple biological organisms to more complex systems, emphasizing ongoing research to uncover biological and molecular mechanisms.

Main takeaways from the video:

Please remember to turn on the CC button to view the subtitles.

Key Vocabularies and Common Phrases:

1. molecular [məˈlɛkjələr] - (adjective) - Relating to or consisting of molecules. - Synonyms: (chemical, atomic, biochemical)

Her work focuses on the molecular and cellular mechanisms underlying the formation, storage, and retrieval of long term memories.

2. consolidation [kənˌsɒlɪˈdeɪʃən] - (noun) - The action or process of making something stronger or more solid; in psychology, the process of stabilizing a memory after learning. - Synonyms: (integration, stabilization, reinforcement)

Once consolidation is completed, the memory is stable

3. implicit [ɪmˈplɪsɪt] - (adjective) - Implied though not plainly expressed; in psychology, relating to memories that are not consciously recalled but influence behavior or emotions. - Synonyms: (understood, inferred, implied)

Then we have the implicit types, and in those we have many.

4. explicit [ɪkˈsplɪsɪt] - (adjective) - Clearly stated or shown; in psychology, relating to memories that are consciously recalled. - Synonyms: (clear, plain, direct)

In the explicit memory systems, we have the memories that we recall consciously.

5. episodic [ˌɛpɪˈsɒdɪk] - (adjective) - Happening in parts or segments; in psychology, relating to memories of personal experiences and specific events in time. - Synonyms: (intermittent, sporadic, periodic)

There are experiential memories, episodic memories of things that we've experienced in our day to day lives

6. neurological [ˌnjʊrəˈlɒdʒɪkəl] - (adjective) - Relating to the anatomy, functions, and disorders of nerves and the nervous system. - Synonyms: (neurophysiological, cerebral, neural)

What about memory that is more for personal identity as opposed to directly for survival? Is it a byproduct of the evolutionary process, or is it just something that complex neurological systems are able to do? It's just one of those things that happens

7. arousal [əˈraʊzəl] - (noun) - The state of being awake and attentive; in psychology, the physiological and psychological state of being alert or responsive to stimuli. - Synonyms: (alertness, stimulation, excitement)

If they are important to you, it means that there is an arousal.

8. schema [ˈskiːmə] - (noun) - A representation of a plan or theory in the form of an outline or model; a mental structure used to organize knowledge. - Synonyms: (framework, blueprint, model)

And, in fact, we see that the learning that they have in infancy creates what we call a schema, because it's something that influences adult behavior.

9. critical period [ˈkrɪtɪkəl ˈpɪriəd] - (noun) - A specific time in development when the brain is particularly receptive to acquiring certain types of information or skills. - Synonyms: (sensitive phase, crucial time, formative window)

And in that temporal window, it's like a critical period.

10. consciousness [ˈkɒnʃəsnɪs] - (noun) - The state of being aware of and responsive to one's surroundings. - Synonyms: (awareness, perception, cognizance)

Those are conscious memories, meaning they require consciousness when we recollect them.

Mind Over Molecules - The Biology of Memory

Our memories define us. They shape who we are. They guide how we act. They connect us to the world. But how well do we understand the pathways in the brain by which memories are imprinted, consolidated, and later retrieved? How does emotion affect the things we remember? And will science ever gain the capacity to tinker with our memories, implanting new ones and erasing things we'd rather forget? And how does the unconscious mind interface with conscious memories? These are but a few of the deep questions that scientists investigating the mind and memory are vigorously exploring. Award-winning professor Christina Alberini is one of the field's leading lights. Dr. Alberini is chaired professor of neuroscience at New York University, where her work focuses on the molecular and cellular mechanisms underlying the formation, storage, and retrieval of long term memories.

Thank you so much. Thank you for joining us. You know, in common language, when we talk about memory in informal terms, you often think of it as this, like singular, monolithic quality characteristic of the brain, that it can make memories. But of course, there seem to be many different kinds of memories from the point of view of experience, right? We have things that we just automatically remember, tying our shoes, how to chew. There are abstract things that we just know about, like the meaning of time and a year, or a cat or a dog. There are experiential memories, episodic memories of things that we've experienced in our day to day lives.

Is there a taxonomy of memories that helps us organize the different types of memories? Absolutely. There are ways to distinguish memories and classify them. For example, according to the duration, we have short term memories and long term memories, and we all experience that. Short term memories, they last for a few seconds or minutes. Long term memories, they last for days, weeks, months, even a lifetime. And we all remember events, single events that happen to us for sometimes the rest of our life. Those obviously are specially long-term memories, and we will discuss about that. Another way to classify them is according to the system, the so-called memory system that processes the information, meaning the learning, the formation of the long-term memories, the storage, the retrieval, and so on.

And there are different memory systems. Two main ones are classified as implicit and explicit memory systems. And in the explicit memory systems, we have the memories that we recall consciously. So if we are here and we memorize today and tomorrow, we can talk about it with our friends, or a week from now or a month from now. Those are conscious memories, meaning they require consciousness when we recollect them. Those are part of the explicit memory system. In those, we have autobiographical memories, we have spatial memories, we have episodic memories, and part of those are also the semantic memories, conceptual memories, memories of some abstract concept. So when I say a dog, you all know what I mean, but you are not thinking of one specific dog. Perhaps you think about one specific dog in an episodic type of memory, a memory of an episode of your life with those details, that specific dog in that context, and so on.

But the concept of dog, which is an abstract concept, comes from learning and is memorized. So those are also different types of memories also belonging to the explicit memory system. Then we have the implicit types, and in those, we have many. I'm not going to go into all the classifications, but the general definition of implicit memories is those memories that when they are recalled, they are recalled in an automatic way without consciousness. So we just, for example, the memories of how to do things, how to tie our shoes, how to ride a bike, and so on and so forth. So those memories are recalled in an unconscious way. They are automatic. We do those actions automatically.

So that is one of the major distinction between the different types of memories, according to memory systems. Memory system means the systems that in our brain process those types of information in terms of learning, storing the information, recalling the information, rearranging the information in the present in order to change, update the memories. We constantly update our memories.

So we're going to dig a little deeper in just a little while. But before we do that, just from a more overview sense, I think everybody can understand the distinct kinds of memories that you just alluded to. How well do we understand the way the brain processes the information that must be distinct, presumably, for these distinct types of memories? Do we understand each pathway? That's a very good question. We actually don't know mechanisms. And now I'm talking about referring more to the biological mechanism. So cell biology, molecular biological mechanism. Genetic mechanisms involved in these memories.

The studies at this level are quite young. They started in the late eighties, early nineties, last century. So we're talking about 30, 40, 50 years, if we consider really the very, very beginning. It's a very young field, and during the first ten years, it was very difficult to get to identifying what are the molecular mechanisms of long-term memories. And so what the field has done is to use very simple systems, invertebrate systems like a sea snail called aplysia californica, or the fruit fly, drosophila melanogaster. Those are two systems that have been very useful to inform us in terms of the genetics and the molecular mechanism of memory from the very early days and from that understanding, then the field went on into studying molecular and biological mechanism in more complex systems, because nothing was known.

So it was very important to start from very simple systems where the number of neurons is very limited, where the tools to ask questions are easier, because the system is very simple. And would you say that there is strong evidence that the mechanisms, the pathways by which memories are formed, are similar across all life on earth? Right. So I was getting to that. Sorry for the long introduction, but, yeah. So from that, then the field went into asking whether those mechanisms found in those systems are also used by more complex systems, meaning different memory systems in more complex organisms.

And it has not been very easy to get the comprehensive understanding of the mechanisms characterizing the different systems. So we just started from what we know from the simple system and just asked the question, are those used also in the more complex systems? Which means we are looking. We are getting what we ask, we are asking whether the same mechanism are used. So we're getting that type of answer. Yes, they are. But so many others which are distinctive, which are not completely known, are certainly to be discovered.

I mean, is it a challenge that the fruit fly can't respond to questioning? They can. No, definitely. There are simple memories that are tested, and we have to consider the question in the evolution, right? Yeah. And so one type of memory that is evolutionarily conserved is or are memories that are important for survival. One of the major questions of memory is to make sure we remember something that is dangerous so that we don't do it again, and we put ourselves in danger all the time.

So if we memorize that and those systems are very, very strong, then we protect ourselves from danger or from disappearing for decreasing the possibility that the species will survive. So survival, simple survival that is present in drosophila, in the fruit fly, in aplysia, in all the simple systems in the C. Elegans in the worm, and as much as in humans. And do you have a clear understanding of the survival value of each of the kinds of memories that you're referring to? Because clearly, if you remember a dangerous episode in your own past, you're less likely to repeat it, which is something that will enhance your survival, pass your genes for doing that onto the next generation and so forth.

What about memory that is more for personal identity as opposed to directly for survival? Is it a byproduct of the evolutionary process, or is it just something that complex neurological systems are able to do? It's just one of those things that happens. The way I see it is everything is coming from an important, an important requirement from evolution. So memories are clearly essential functions for survival and for everything we do every day. So one is to protect ourselves from danger, but the other one is to find the best resources for the most adaptive behavior that every day we have to do.

In that there is also what memory does to each individual, which is creating a system that is very individualized. And it is very individualized because we learn every day in different ways in different contexts. So why this individualization is important in evolution is that if we are transported in another place, in a different context, where we have to adapt to that context, and we're going to do that through learning, we have to be able to do so. So in other words, we are who we are because of our memories, memories in the large sense, implicit and explicit types, memories that change every day, that change according to the new experience. So we have a lot of storage of information, recall of information, and then new learning in the context of what we have learned. And this happens throughout life.

Just think for a moment, what will be your life without memories? It cannot exist. Simply it cannot exist. So it's an essential function, but it works in a way that every day we are learning something new, and we place that new information into the history of our system. And that is the memory, meaning the storage of information.

And of course, there are pernicious diseases which rob us of memories. Do you think of those at all in an evolutionary sense? Because after all, if memory is evolutionarily part of our strategy for survival after we pass the age of reproduction, the disintegration of memory should have no impact. And then why would the body waste energy on preserving these memories when it doesn't need to preserve you for survival any longer? Is that a useful way of thinking?

Yeah, and I don't have the answer for that. Right? Because if we think about evolution and survival after we reproduce, what's the use of it? But I would think that the use is to help the group, the species, to be in a better adaptive context. So this, and this is, you know, there is no real proof for that. But logically, we can think that in groups, we create conditions that are more adaptive or can resolve certain problems that we face in a different way than just the individual would do.

So that would be my answer. And it's important to think about memories throughout life at different ages because they're different. So memories of a newborn learning, and memories in a newborn clearly are very different than learning a memory when we grow up and we are at a different age, but still very young or adolescents or young adults or middle aged or aged. And each of these stages clearly comes with a different biology.

So what we are very interested in studying is the biology that changes throughout different ages, and how this biology is used by the memory system to create new memories, to recall old memories, to create new learning in the history and adapt it. So, digging down on that, if we can just maybe do an example, almost an exercise. So everybody in this room is experiencing the conversation that we're having. Hopefully it's forming memories, hopefully long term memories, so it doesn't just go out of mind an hour from now, if that is happening inside the brain of either a person watching this live or digitally, can you take us through in broad brush or microscopic detail, whatever you choose, what's actually happening inside the head of someone who is forming a memory of our conversation?

Right. So memories of an episode like this will become long term if they are important to you. If they are important to you, it means that there is an arousal. It means that some hormones and neurotransmitters that are important for processing attention, arousal, excitement, are released in the brain. So those systems talk to the memory systems. So other networks of cells, not only neurons, neural science is very centered on neurons, which is rightly so.

However, there are many other types of cells in the brain, and they all cooperate for all these processes that happens. What happens is that these hormones and systems that modulate the memory systems themselves. So the network of cells that store and storage, actually, I'm going to go back to this, that store the information on turn, they create biological changes over time, it takes time to form memories. So this memory that you form today, no matter how long term, is going to be, but let's say it will be a long term memory is not now stored in a strong way.

Right now, there is a representation of what's going on here, which is actually fairly detailed, because you know what I'm saying, what Brian is asking, who is around you? You see the details of the room and so on and so forth. But this is not the long term memory that will last. A number of changes happen in the brain based on biological activation of pathways. For example, there is gene expression, transcription and translation. Those are the two major mechanisms in biology, transcription of genes.

Translation of mRNA's are essential for long term memories. So the way we distinguish long term memories from short term memories is by looking at whether they require transcription and translation. This is a hallmark of long term memories. So transcription, translation happens in our circuitry of memory, circuitry of episodic type of memories. One major region involved is the hippocampus.

But the hippocampus crosstalk to many others cortical regions and other regions, they get the input or the regulation, the modulation from amygdala, for example, from other areas of the brain that tells that this is an important event to memorize. And all those molecular changes in all those brain regions, they change over time. The first 24 hours are very important, but they continue to happen for days, and in some cases, also weeks. Weeks that meaning that the hippocampus and cortical regions, for example, reverberate, keeps talking to each other. And all that biology that occurs over all this time is essential for forming long term memories.

If there is an interruption of those mechanisms, long term memories are not going to be formed. The earlier the interruption is the disruption, the more the long term memory will be absent, will be disrupted. So in other words, there is a cascade of molecular events that happens in the brain that over time create a stable representation. And this stable representation changes, as I mentioned, over time and over weeks, it shifts from certain regions to others until it becomes these memories, is called consolidated.

So in other words, memories are fragile when they're formed. Over time, they consolidate. Once consolidation is completed, the memory is stable. And if we try to interfere with the molecular mechanism, there is no effect anymore. The memories of now, you mentioned transcription and translation as a vital part of going from short term memory to long term memory. And so that's the production of certain proteins, presumably.

Do we understand how the production of those proteins are essential to the memory moving to the long term phase? Do we understand that? Well, at the molecular level? Well, it's too much. It's pushing it. But certainly this was one of the questions that started, as I mentioned, in the late eighties, to understand what molecules, what genes are expressed to form long term memories, what proteins are made, where do they go, what do they do exactly in the brain? For how long are these mechanisms involved? And so on and so forth. And of course, we have addressed some of the questions, but not all of them. So there is this cascade of gene expression. So a number of genes are transcribed and then translated into proteins.

There are also many other levels of regulation, chromatin changes. Of course, when there is gene expression, there is also chromatin changes, and also the transcription of rna's that are not translated into proteins, but regulate a number of steps. So there are so many steps at the biological level that converge into a cascade of mechanisms. My lab, as many others, have focused on which transcription factors and genes are transcribed in the brain. In these brain regions, which are required for long term memories. And many others have looked at the translation of this mRNA. So we and others, of course, have identified a number of mechanisms of pathways that are essential for long term memory formation, long term memory storage, as well as whether they are re involved when we recall memories. That's another interesting, well, I wanted to ask you about that memory because from an experiential standpoint, just anecdotally, when I've wanted to remember something long term, even when I was a student, what I would do is 15 minutes before the next lecture, I would review the previous lecture. And I found just by reimagining and rethinking about the material from the previous, it just stuck in a way that was more potent for me than cramming it in at the end.

And when I have to, you know, give some kind of presentation, I want to remember this or that, I find just a little ten minute reminder every single day. Is what makes it go from short to long. Is that consistent with your understanding of how long term memory is formed? It is. It is. We have studied what recalling memory does when we recall memories, of course, is, you know, intuitively we recall memories because we need to do something, we need to make a decision. But what happens in the memory system and why is this recall important? And it is important, as we found, to strengthen memories, but clearly the recall is not as the learning event.

So it's a different processing of the memory is not exactly strengthening completely the memory that we originally had in the learning event, but we recall, and perhaps is a partial recall, and that is strengthening the memory. This is also what we found. But when this was studied in terms of molecular mechanism, it became very interesting because so, as I mentioned, long term memory requires gene expression, and it was believed that once memory is consolidated, is no longer sensitive to disruption or changes. Of course, it can be changed with new learning, but a number of studies show that when memories are recalled, they become fragile again for a limited temporal window, similar to what happens with no learning. And during the temporal window again, they require transcription, translation to stabilize. In other words, there is a reconsolidation happening with the retrieval, the recall of the memory.

So memory recall can be dangerous then, in a way, this doesn't happen with all the memories and all the time, but it happens, and so it can be dangerous, right? So why should it be? If it is dangerous, why actually does it happen? Nature doesn't work that way. It happens because with that fragility, we can actually strengthen the memory. So it is a way to, it's like a tradeoff, strengthen the memory. To trade off, you go into a danger zone of modifying or losing the memory.

But the upside is, by undergoing this process, you strengthen it if it's survived, right? In most cases, you will not lose it. You have to interfere in order to lose it. In other words, new learning could do that, could interfere. And this is why memories are not precise, because constantly we recall memories, we have some new learning coming in and also decays of memories. Forgetting is another process of memory, of course, very important. We need to forget. So all the combination of these creates the way memories work, but they cannot be precise because we constantly change them.

So another way through which these recall dependent changes work is to incorporate new information into the old representation. So we recall, and now we associate something new to that. So this mechanism or process is called reconsolidation. It has been studied quite a bit. It generated a lot of interest, particularly if we want to think about, for example, diseases like post-traumatic stress disorder or addiction, where the memories are very strong memories of trauma, and they're also very distinct, right? Distinct from normal memories, post-traumatic stress or addiction. The memories of how the substance feels is very much connected to context. People who are addicted relapse when they go back to the old context, because the memories of it make them relapse. So there was a lot of interest when this reconsolidation and temporal window of intervention, let's call it, emerged because the field thought it could be an interesting approach to actually decrease the strength of those memories and help the process of therapeutics.

So, I don't remember the mechanism in eternal sunshine of the spotless mind. But was that the basic idea, that they were restimulating the memory and getting in there, and somehow it's exactly like that? It is exactly that. We see this in the lab. So if we take an animal, we work with rats and mice, with rodents, we take an animal, they learn something, and then we make them recall that memory. And during the temporal window of reconsolidation, we intervene. It can be in different ways to interfere with the reconsolidation process. They forget, not that they forget, they lose the memory because they cannot reconsolidate it. So the memory, they can't run through the maze anymore or something like that, the memory decreases.

Wow. Now, you also made reference to emotion being an important part of long term memory formation. So, and I don't mean this to sound facetious, but I'm actually wondering. So, you know, if I'm studying general relativity, I'm at my desk and I'm usually pretty calm as I'm going through the ideas in the equation, say. But if I was to somehow be much more excited and emotionally disturbed or in some frenzy state, is there a better chance that I will remember the material in a long term way? For sure. But you know we know that, right? Even caffeine, right? I don't want to mention other stuff. No, feel free.

We already have these examples throughout many years. We know that. See, I would have always thought caffeine or artificial stimulants were viewed. And I'm learning in this conversation, they, to me, were just focusing your attention more fully because you're more awake. But not because you're emotionally aroused. No, but attention is one way to increase the storage of long term memories. The other is arousal, as you say. So is a similar consequence. These hormones can increase, do increase the biological changes, as I was mentioning, happening in the memory system, which lead to morphological changes.

In other words, there is a physical change in the brain, in those circuitry that store memories, as my advisor used to say. I train at Columbia with Ari Kandel. After an event, if you form a long term memory, you have another wrinkle in your brain.

So just thinking about the wrinkles for a moment. If one is trying to enhance long term memory, which I think many of us want to do, I mean, it's very frustrating. You learn something, and then a week later, you just can't grab ahold of it. What are the effects of other things like sleep or dreaming? Does that have an impact on our capacity to retain information? Some people say study it just before you go to sleep in order that the brain can consolidate. Is that real? Is there evidence for that?

So there are evidence. The most, I think, interesting evidence for students is that do not cram. Because in order to form a long-term memory, the brain needs time. As I said, this is a process of biology that requires time, memory consolidation. If you go right after your learning with another learning event, another consolidation process is going to start. Then the brain is confused. You're not going to remember well which is the first learning piece or the second learning. And these experiments have been done more than 100 years ago shown.

So that's called retroactive interference. If you go with a second learning event too close to the first one, the two events are not going to be remembered well in a separate way. So do not give time. Now, sleep is very important. That's very well known that if sleep or circadian rhythmicity is altered, consolidation is going to be impacted because those mechanisms of circadian rhythmicity and sleep, they work together with the consolidation process.

The biology that I mentioned, all that cascade includes a number of modifications that happens through the circadian rhythm, as well as what happens in sleep, where the representation is replayed. So this replay is important for the consolidation. So if we disrupt the biology is part of these processes. If we disrupt any of these processes, and we can go with the biological mechanism, or. Or no learning or behavioral approaches, then we disrupt the ability of the brain to form long term memories in the best way.

Now, can we enhance memories? We can. We have found molecular mechanisms that can do that very nicely. One example we have in the lab is it's a small protein. It's called insulin-like growth fat factor two, IGF two, insulin-like growth factor two, and IGF two belongs to a family, together with another IGF, IGF one, and insulin.

But these three proteins, they have very different functions. And IGF two we discover to be regulated in brain regions important for long term memory, like the hippocampus. Hippocampus with learning, and to be required for long term memory formation. In other words, if this production of IGF two that occurs in the hippocampus with learning is blocked, long term memories do not form. So it's required.

Can you do it artificially? Can you add? And then we add it. So you can deplete the system, or you can add. Right. So then when we added IGF two, without interfering with anything else, just having the learning event, the memories were spectacularly stronger and longer-lasting. This is in rats. This is in rats and mice.

And this small peptides protein can actually be injected even systemically, like insulin can be injected subcutaneously. We can do that with IGF two. And we have these animals that have a super memory very strong and long-lasting, significant effect.

So then, of course, we became interested in studying memory enhancement in the normal animals, but also whether this could be a potential therapeutics for memory disorders. We have an incredible need for novel therapeutics that can work for memory disorders.

And you've not tried on people? And we have not tried on people, but I started a company because the data that we have seen in the lab.

Are you taking investors? I do. So this IGF two reverses not only cognitive impairment. So we in the lab, we have tested aged animals, and the cognitive impairments related to aging is reversed. We tested models of neurodevelopmental disease disorders like autism. Angelman syndrome is a genetic neurodevelopmental disorder, and these are characterized by cognitive impairments. So we reverse the cognitive impairments, but also the other problems that they have. And that was very exciting, but also surprising, I have to say.

For example, in Angelman syndrome, they have motor problems in addition to cognitive problems, they have repetitive behaviors like autism. They often have seizures. And with IGF two, we reverse all of these. So it sounds like a miracle, but it must be a downside, right?

Exactly. So we started testing. What are the downsides? Do we see, for example, the memory that are potentiated in the normal animals? Are they more rigid? No, they are nothing. Do we see any obvious side effect? We have not seen, but, of course, these have to be tested in a different way if we want to go to people. Of course.

So, so far, it's really very exciting, what we see with this IGF two, not only as a cognitive enhancer in normal individuals or normal animals, but also as a potential therapeutics for a number of diseases. So what do they have in common? Aging, for example, aging-related cognitive impairment with neurodevelopmental disorders. And other labs have studied IGF two in Alzheimer's disease models, in Huntington's disease models, and, again, all beneficial effects with IGF two.

What do they have in common? They have in common that they accumulate proteins in the brain, different types of proteins in different diseases. But the common problem is protein accumulation in the brain. So we were very surprised to see all these effects, and, of course, went into studying the mechanism for why this may happen. And it turned out that this IGF two works through a receptor that regulates protein metabolism, in other words, the making and breaking of proteins and speeds up protein degradation.

That is, the elimination of proteins in the protein metabolism. Is that like eliminating plaque? Is that a different type of thing? So that's what we want to do now. We want to look at whether, in the disease models, we eliminate those specific proteins, let's say Alzheimer's disease models that we see plaque elimination and so on and so forth. Some studies already have shown that that's the case with IGF two in the mouse model. So it's very exciting. It sounds it.

I want to just change gears a little bit. One of the interesting realizations in the last few decades in the judicial system is how unreliable eyewitness memory and testimony can be. How do you view that from a neuroscience memory perspective? Indeed, we already touched upon that. Memories are not accurate. I think, first of all, from my personal point of view, we have to distinguish between what happened and the accuracy of memory, right?

Sure. I mean, if somebody comes up with something that never happened is different than saying, oh, I have seen that person that day in that place. This is where memories are not accurate because over time and many rounds of similar memories, for example, if you return to this room ten times, you will confuse who was at which time in this room. And clearly this information is going to be less and less accurate as time passes. So if I ask you tomorrow, you have a more accurate memory, but if I ask you a month from now or six months from now, the memory is going to be less accurate.

Considering that the repetition and the amount of information that we have to make sense with and what we do, you can imagine how the information is confused in terms of who is in a certain place at a certain time. And so this is where the memories are not accurate. We usually say, you know, if you talk to your family about a new Year's Eve together, I don't know, some festivity together, and you start talking about who was there and what was said, there is a complete disagreement about the members of the family, especially if the event is dated. Right?

So over time the information gets confused and that's why the memories are not accurate. So, yes, they can be. And do you imagine that memories that are, say, inaccurate or degraded or people completely forget, is the root information still somewhere in the brain?

I mean, like a Freudian perspective would say, it's always there, it's always influencing you, even from times that you don't even consciously remember. Is that a kind of Freudian myth or is there evidence that everything that's ever happened to you is somehow stored someplace and is affecting you in some manner? Yeah.

So I don't know. I don't know how to answer that question. The Freudian essence. So to me it's different. I actually, at one point in my life, trained as a psychoanalyst. So I started as a biologist, I'm a molecular biologist and I keep doing that. But at one point I studied as a psychoanalyst, and that essence, to me, and this is what influenced my studies in the lab, actually comes from development.

So we are switching a little bit gears here. It's not this. Everything is in our brain and everything we do is stored long term and it can appear later. I think actually the unconscious, but this is my interpretation, I think the unconscious that Freud is talking about that influences our life throughout comes from development. The way we learn from day one, even before the learning that happens through development is shaping the brain and the systems.

And I have started to study that. That's why I became interested in studying the biology of learning and memory in infancy. So we take infant rats and mice and look at the biology when they learn. And what we found, it was also very interesting and not predicted. So we went into the question without any mindset. What we found is that, in fact, the brain in infancy is learning to learn for a certain temporal window. And in that temporal window, it's like a critical period. It's a critical period. That's exactly it.

In that critical period, the system is developing and shaping according to the experience that the animal has. That's the basis of individuality. So it's not the specific details of the memory, it's rather how the experience shaped the way the brain will subsequently function. And it's open to that influence during this critical period. And, in fact, we see that the learning that they have in infancy creates what we call a schema, because it's something that influences adult behavior, and it influences, in a way that, first, the memory can be reinstated.

I'm going to get back to that, the infant memory, and secondly, it influences similar types of behavior. And this happens only with the learning during that critical period.

So the reason why we concluded that there is a critical period is because we tested it. When we started to look at this biology, it was believed that learning in infancy is forgotten, and this is true. So what do you remember of the first three years of your life? But this is normal. So this rapid forgetting that happens in this phase of infancy is believed to explain what is called infantile amnesia, the fact that as adults, we don't remember the first few years of life. Theories and what was known at that time.

When we started to investigate this, they were suggesting that consolidation doesn't work because the memory system that uses the hippocampus is not developed. The hippocampus is not involved, it's offline. So we started to give these infant rattomized learning events and then tested whether the memories could come back. So that was the first question, right? If it's gone, it's not going to come back. We were able to see it coming back, coming back. It comes back.

So the animal forgets, because when you test them, they show no memory. Like humans, there's a very rapid forgetting, no memory. But if you then later on, test them with certain type of reminders, you can get the memory back. And you knew the specific reminder because you set up the situation. Yes, but we tested a number of them before, but for us, we wouldn't know how to do that. But no, we don't know.

And also, it's unclear whether those memories that come back are conscious, meaning they are conscious when they come back. But are they conscious about when they were learned?

We have no way to test it. My view now is that those are implicit type of representation, implicit type of memories, not explicit. I see that. However, later on, they are recalled, reactivated with some new learning or some reminder, and then they create the expression of the explicit memory. But they influence what we do.

They influence what the animal does in adulthood, for example. We didn't test in the old age, but up to adulthood for sure. I can say that. So, the reason why we concluded it's a critical period is because we tested the biology of that hippocampus and found that molecular mechanisms that were identified by other studies in the sensory system as mechanism of critical period are used by our system, the memory system, to form these long term memories that are not expressed, but they can return and they influence adult behavior.

That's kind of amazing. Unfortunately, we only have a couple minutes left. I wanted to ask you a few more questions just to get your quick thoughts on these issues. I think many of us have had the experience that music is an incredibly powerful way of bringing us back to an emotional state at some earlier time in our lives. Do we understand why music has that capacity here is out of my expertise.

But there are groups studying music and how that influences brain activities and how that influences why, you know, we have this. Why we have this very strong recall with emotion is because music is a cue and that is processed by amygdala. So there is a representation that is directly linked to the emotional systems, basically. But more than this, I cannot really say, because it's not what I'm studying. But, yeah, there are several studies going on with another question that may fall into that category, if you don't mind.

So, some of the greatest literature has explored human memory in various aspects and approach. Is there. Is there a book out there that you consider to be one that really, in an artful way, captures the wonders and mysteries of memory? Is there anyone that comes to mind? Unfair question. No. No, I would not even mention any, because there are. You know, I would say there are several with different.

From different angles in different ways. Yeah, sure. And a final thing, the world is extremely excited about artificial intelligence now, and it's a wide open arena. But do you see those developments interfacing or intersecting with the kind of work that you do on the natural version of intelligence and memory? They're already working together. So artificial intelligence is very much involved. For example, computational work is very much involved in understanding now all the types of mechanisms that are active in certain brain regions and how do they change and so on and so forth.

So data analysis, because a lot of approaches now, they are not looking at single mechanism, they are looking at the comprehensive pattern. So this is where computational comes in. There are other ways to manipulate brain circuitry. Again, is engineering certain mechanisms and creating artificial tools that can change the circuitry in the brain and therefore behaviors. These are just two examples, but there is a lot also done in terms of theories that we thought that hopefully will inform experimenters how to test new questions about understanding the mechanism of memory.

And can you imagine, just oblique to that, but resonating with it, will there be brain machine interfaces that enhance human memory? Is that a direction that you see bearing fruit? I don't know. I mean, in theory, yes, but I don't know how easy that will be because biologically, considering the biology of it, which is where I come from, the brain constantly changes. And this adaptability to whatever change comes in the environment is very difficult to recreate in a machine. So we can create circuitry, we can create, we can plug in a number of information.

It can be extremely sophisticated, but how can we predict something we don't know? So that's the bias, I think. Yeah, absolutely. Well, it's been a fascinating conversation on memory across the various forms of life with that capacity. Thank you so much, and please join me in thanking Christina Alvarini. Thank you so much.

Science, Education, Technology, Neuroscience, Memory, Brain, World Science Festival