Space and memory

This week on From Our Neurons to Yours, we sit down with Stanford neurobiologist Lisa Giocomo to explore the intersection of memory and navigation.

Feb 22 2024

Nicholas Weiler

From Our Neurons to Yours Wu Tsai Neuro Podcast

This episode was inspired by the idea of memory palaces. The idea is simple: Take a place you're very familiar with, say the house you grew up in, and place information you want to remember in different locations within that space. When it's time to remember those things, you can mentally walk through that space and retrieve those items.

This ancient technique reveals something very fundamental about how our brains work. It turns out that the same parts of the brain are responsible both for memory and for navigating through the world.

Scientists are learning more and more about these systems and the connections between them, and it's revealing surprising insights about how we build the narrative of our lives, how we turn our environments into an internal model of who we are and where we fit into the world.

Join us to learn more about the neuroscience of space and memory.

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About Lisa Giocomo’s research
About the story of Henry Molaison (patient H. M.), who lost the ability to form new memories after epilepsy treatment removed his hippocampus.
About the 2014 Nobel Prize in medicine, awarded to John O’Keefe and to May-Britt and Edvard Moser (Giocomo’s mentors) for their discovery of the GPS system of the brain
About Memory Palaces, a technique used since ancient times to enhance memory using mental maps.

Episode credits

This episode was produced by Michael Osborne at 14th Street Studios, with production assistance by Morgan Honaker. Our logo is by Aimee Garza. The show is hosted by Nicholas Weiler at Stanford's Wu Tsai Neurosciences Institute.

If you're enjoying our show, please take a moment to give us a review on your podcast app of choice and share this episode with your friends. That's how we grow as a show and bring the stories of the frontiers of neuroscience to a wider audience.

Episode Transcript

Nicholas Weiler:

This is From Our Neurons to Yours from the Wu Tsai Neurosciences Institute at Stanford University. Each week we bring you to the frontiers of brain science, to meet the scientists unlocking the mysteries of the mind and building the tools that will let us communicate better with our brains. This week, memory maps.

I was inspired to do a show on this topic because I've always been fascinated with the idea of memory palaces. If you're not familiar with this idea, it's basically a technique for improving your memory. And what you do is you take a place you're very familiar with, say the house you grew up in, and you place pieces of information that you're trying to memorize in different locations within that space. Let's say you're studying for an organic chemistry test and you might put different chemical compounds in your bedside table, under your bed or behind the closet door. And then when it's time to remember those things, you can mentally walk through that space and retrieve those items. This is actually a very ancient technique. Similar techniques were used by storytellers from ancient times to memorize epics like the Iliad and the Odyssey. And this was popularized by Arthur Conan Doyle and his stories of Sherlock Holmes.

This ancient technique actually reveals something very fundamental about how our brains work. It turns out that the same parts of the brain are responsible both for memory and for navigating through the world, for building maps of our environment. Scientists are learning more and more about these systems and the connections between them, and it's revealing surprising insights about how we build the narrative of our lives, how we turn our environments into an internal model of who we are and where we fit into the world. I wanted to learn more about the underlying neuroscience, which brings me to today's guest.

Lisa Giocomo:

My name is Lisa Giocomo, and my lab studies memory and navigation, the classic example being how you know where you parked your car in a parking lot and how you navigate back to that location.

Nicholas Weiler:

That's a perfect example of exactly what I'm excited to talk about today. These two fundamental processes in our mental lives that I think intuitively seem quite different, but actually have a surprising amount in common. On the one hand, there's our ability to record memories of events from our daily lives, and on the other, there's our sense of our physical location in space, our ability to navigate through the world. And it turns out that both of these capacities rely on structures deep in the brain's temporal lobes called the hippocampus and the entorhinal cortex. So before we get into this big question about how is memory and navigation linked in the brain, maybe we could talk about each of them one at a time. Do you mind telling us a little bit about how researchers discovered the hippocampus's role in forming new memories?

Lisa Giocomo:

Yeah, so one of the really pivotal moments in hippocampal research came from a clinical study on a particular patient named H.M. H.M. had intractable epilepsy, meaning he had epilepsy that was not treatable. And so a decision was made to remove the parts of his brain that were the focus of the epileptic seizures, and that was his hippocampus and some of the surrounding areas. He had this surgery done when he was a young man, and at the time it wasn't really well understood what exactly the hippocampus contributed to. And so it was a bit surprising then to clinicians that after the surgery he was no longer able to formulate new episodic memories, memories for events that were sort of combinations of people, places and things. So he could remember quite well events from his childhood. He could remember things that happened five years before the surgery, but he couldn't actually remember anything very close to the surgery and anything that happened after the surgery.

And I can give you an example of a vignette that Brenda Milner shared who was the main researcher that worked with him, where she went into his room and was going to perform some memory tests with him and asked him to remember a series of five or seven numbers, 4, 6, 7, 5, 2. This is considered what we call now a working memory task. So I can give you those numbers and then I can wait a few seconds and I can ask you to repeat them. Most people when they perform this type of task will kind of keep that number set running in their brain. And so she gave him a set of numbers and a few seconds later said, "What are the numbers?" And he repeated the numbers back. And then she gave him another set of numbers and waited a minute or two, and he repeated the numbers back.

And then she gave him a third set of numbers and said, "Okay, I'm going to leave the room. I'm going to get a cup of coffee and I'll come back and ask you the numbers when I return." And as soon as she left the room, he was distracted. When she came back into the room, she said, "Can you tell me the numbers?" And he said, "What numbers? Who are you? And I didn't order any coffee."

So he was able to have this very rapid kind of online ability to keep something in mind, but he couldn't get that then into this longer term memory storage. So as soon as it was lost from that online, it was just gone forever.

Nicholas Weiler:

Yeah, that's fascinating. I mean, it's so interesting because we talk about memory in a lot of different ways, but there are very different types of memory in our brains. We can remember facts and figures. We can remember the dates of important events, and we can remember how to ride a bike or how to play the piano, and we can remember something that someone just told us, but the kind of memory that we're talking about is sort of the story of what's been happening to you. And that's why, I guess we call it narrative memory.

Lisa Giocomo:

That's right. So H.M. was actually also the case that really led us to understand that different kinds of memory depend on different parts of the brain. So remembering to play the piano or remembering how to throw a ball don't rely on the hippocampus. This narrative memory is crucially dependent on the hippocampus as is to a pretty large degree semantic memory. So H.M. also struggled to learn new facts about the world. He still thought that the year was the year that he had the surgery. So these two components of memory, both narrative or sometimes it's called autobiographical or episodic memory, the kind of movie memory that if I think about what I did during the day, that kind of memory is just really critically dependent on the hippocampus.

Nicholas Weiler:

Now I want to discuss the later discoveries that the hippocampus is also critically involved in our ability to navigate through the world.

Lisa Giocomo:

I think H.M. generated a lot of interest in the hippocampus.

Nicholas Weiler:

And this was in the 1950s?

Lisa Giocomo:

Yeah, 1950s. And sort of the question then became what does the hippocampus do? And so John O'Keefe in 1971 put electrodes into the brains of rats, and he put rats into a maze. And what he found was quite astonishing. He found that there were individual brain cells, single brain cells in the hippocampus that were really active only in one place in that maze. And because of that, they were called place cells. For example, if I think about being in my house, I have a place cell that's active when I'm in my kitchen. I have a place cell that's active when I'm in my bedroom. I have a place cell that's active when I'm in my hallway. And the idea was that these place cells as a group of cells can basically allow you to form a map of the world. So they allow you to build a map of the room that you're in and of the local environment. And so that became really kind of a push for the narrative that the hippocampus is important for memory of course, but it also has this really large role in understanding your spatial world.

Nicholas Weiler:

And we've come to learn more and more about this navigational system. There are all kinds of specialized cells, not just the place cells, but those are built on a neural vocabulary of different aspects of where we are, what direction we're facing, which way our head is going, which way we're moving. How has that helped us understand how this picture of where we are in space was built?

Lisa Giocomo:

Over the last several decades, all of the substrates needed for you to build a map of space have been discovered in the hippocampus and surrounding regions like the entorhinal cortex. So if you think about a map on Google Maps, for example, there's a few different features of that map that are really important. There's a longitude and latitude coordinate system, and it turns out there are cells in the brain called grid cells that provide that type of coordinate system. There are landmarks on that map. There are a number of different cells in the brain that tell you where objects are in the world. There are routes, there's roads, kind of an understanding of boundaries, and there are cells in the brain that tell you where borders and boundaries are in the world.

And then as you begin to navigate through that map, if you're looking at a map of campus and you're trying to walk across campus, as you navigate, there's additional information that you might be gathering. You might have a compass, for example, so whether you're traveling north or south, and it turns out there are neurons in the brain that operate like a compass. And you might also need to know the speed that you're traveling so that you have a general estimate of how long it's going to take you to get from building A to building B. Are you walking, are you jogging? And there are neurons in the brain that act as that type of speedometer. The way we think about it is that all of these neurons basically allow your brain to build an internal map of your external world.

Nicholas Weiler:

That's such a fascinating system. I mean, it feels so mechanical, at least now that we have all of these tools on our phones, like you said, with Google Maps or a GPS system. It's amazing that all of that is going on in our heads too, but it does feel intuitively very different from how I think about my ability to remember what I did yesterday. Help me understand how those things are connected. How do the memory systems and navigation systems interact with one another?

Lisa Giocomo:

Yeah, I think there's a few different ways you can think about their interaction. The first is that if you think about a memory, there's often a strong spatial component. If I think about what I had for breakfast, it's typically in the context of where I had my breakfast. So that's one way in which we think of these memory and navigation systems interacting. The second is sort of as a complimentary type of process. So finding your way back to where you parked your car, for example, it requires a memory of where you parked your car, which is sort of a multisensory, maybe you remember some landmarks around it or the distance that you traveled from your car to the store. But then as you exit the store, you also have to navigate back to that location, and you may even have to do that flexibly. Maybe you exit the store from a different location from where you entered. And so your navigation system really has to interface with your memory system for you to execute that behavior.

And the third is that in humans, when we think about navigation, sometimes we actually think about navigation in a non-spatial context. If I am imagining where I'm going to go, there has been really interesting work showing in humans that the same navigation system is active when humans are imagining paths in which they may travel and when they're actually navigating through those paths, say in virtual reality. In that sense, especially in the primate brain or in the human brain, the navigation system is leveraged not just for finding your way from your borough to a food source, but it's actually leveraged in much more cognitive processes like imagination or I remember where my house is. I can imagine the route that I need to take to my house, and that helps me with kind of planning and decision making in the future.

Nicholas Weiler:

Yeah, I love that. And you could imagine having a system for navigation, which is something that all kinds of animals that move around need, and that as that gets more and more detailed, there's this sense in which events in our lives are almost like landmarks in time. Not to get too woo-woo about it, but you can see that understanding where you're going and where you've been. You also sort of need to know what happened where, like, "Oh, that's the spot where I got attacked by a hungry wolf. Maybe don't go that way." So there is this interesting connection between what happened and where you are.

Lisa Giocomo:

Yeah, that's right.

Nicholas Weiler:

I mean, is there any evidence about which came first navigation or memory, or is that something that we don't have a good handle on?

Lisa Giocomo:

Yeah, that's a really great question. It seems like different components of the navigation and memory system come online at slightly different ages. This has never been studied in humans, but rodents have an internal compass even before they open their eyes. So they have a sense of how much their head is rotating and how that might translate to the direction that they're facing. And that could be adaptive in the sense that if you're a nursing rat pup, you need to be able to orient yourself in order to find your food source. After that, it seems like some very basic play cells come online. They don't quite have the same qualities that you see in adulthood, but as animals gain a little bit more experience with the environment, you start to see some of these longitude and latitude coordinate system cells come online.

It's not fully understood yet how that system or exactly what day that system kind of comes online, but it may take a little bit longer for that internal coordinate system to really get tethered to the external world. In humans, I don't think that developmental timeline is known really at all, but there's reason to believe that same kind of progression of development may be similar across species.

Nicholas Weiler:

Right. Well, I mean we know that children are able to navigate long before they're forming long-term memories.

Lisa Giocomo:

Well, there is the phenomenon of childhood amnesia. So if you ask a 2-year-old about something that happened a month ago, they can have a very good memory for it. I mean, I have young kids and when they were two and a half years old, they 100% remembered the time we went to get the ice cream cone four months ago. And something that I said about how I promised we would go back.

Nicholas Weiler:

Right, absolutely.

Lisa Giocomo:

But that is lost around the ages of four to five. There is some kind of process that is not well understood by which we retain very few memories from those early childhood days. But that doesn't mean that children at that age aren't capable of long-term memory. There's a lot of interesting hypotheses about why this happens, but around that age, there is a loss of memory that happens for those early childhood days.

Nicholas Weiler:

So there's been this whole line of work that your lab is connected with. I first heard about it in some studies about animals when they're asleep, and animals when they're moving through an environment, but maybe taking a rest or thinking about where they're going to go next. And that these place cells kind of fire either in a forward direction or even in a reverse direction as if going back over the steps that an animal took to get somewhere. So that also gives us a sense of the connection between navigation, moving through space, and creating memories and planning as you said before. Like what am I going to do? Where have I been? Where am I now? All of these things are critical for an animal's behavior.

I wonder if you could just talk a little bit about the fact that we can now essentially observe through modern recording techniques, these maps live as animals are moving around. We can see their internal model of the space that they're in. And how your lab has been looking at that to try to understand how these maps change depending on the animal's behavior, their physical state or what they're trying to accomplish.

Lisa Giocomo:

When I was a PhD student, when I was a postdoc, you were trying to look at the activity of maybe 10 cells, 10 neurons at the same time. And while that's really informative, these internal spatial maps are made up thousands of neurons. And unless you can look at many neurons at the same time, it's really hard to look at questions like how these maps develop. How does something that the animal learns about the environment changing these maps or being incorporated into these maps? How do these maps change as we age? These are all questions that really require lots and lots of neurons. They're very hard to answer with just 10 to 15 neurons. And a new silicon probe technology has really facilitated this. We can record from hundreds of neurons simultaneously within a single animal. We can record from thousands of neurons.

And I think one of the things that we've been really excited to see is, so if we have an animal in an environment and it's wandering around and we suddenly drop in a very large Cheerio, which is a large exciting reward to a rodent, the internal spatial map of the rodent will actually change and it will start to have a better map, a more detailed map, and it may even have a lower resolution map for the area that's further from the reward. We think that may enable the animal to later remember that location better. If you imagine a rodent foraging through a large forest or even a rodent in your house, the rodent might want a much better map of your kitchen, even if that means it doesn't have a great map for your bedroom where it never finds food there, but it finds a lot of really wonderful food sources in your kitchen.

Nicholas Weiler:

Well, the brain is powerful, but it still has to prioritize.

Lisa Giocomo:

That's right. Exactly.

Nicholas Weiler:

When you're talking about the resolution, the fineness of the map, are you talking about almost the pixel size of the neurons or the pixels?

Lisa Giocomo:

Yeah, you can think of it that way honestly. If you had a map that was an image, one portion of the map might actually have more pixels, richer information, maybe more landmark information, whereas the other part of the map is maybe a little bit fuzzier, or maybe it has less information, but maybe it doesn't matter. You never really go there. You don't really need that much information. But when you get to this location where there are many restaurants that are your favorite restaurants, you really want a great map for that. You want a high resolution map where you can easily navigate up to your favorite coffee spot and then down to your favorite dessert location.

Nicholas Weiler:

Right. Oh, I'm getting hungry now. But then you've also been doing work that's showing how animals may have more than one map of a given location. There may be multiple maps. Can you tell me a little bit about what that might mean?

Lisa Giocomo:

Yeah, yeah. So that was a really exciting and actually very unexpected discovery. We had always operated under the assumption that there was one map, and using these silicon probes we could record from many cells. We actually observed that there was not one map, there were two maps, sometimes three maps, sometimes four maps. These maps would come online, come offline. The way that we were sort of imagining it was that you may have a different map depending on what you're trying to do. So imagine you are headed to the mall and you want to go directly to a particular store. You may have a map that's actually adapted for that. It maybe has a really high resolution route to the store. Maybe it has particular landmark information that's a little bit more salient.

But let's say then you go to the mall and you don't have any particular destination in mind. You just want to wander around and see what's there. That may be a different map. That map may have a medium level of resolution and allow you to more flexibly navigate or randomly forage through the environment. Whereas the first map is really adapted to be very specific to something that you're trying to do. You want to go to this one particular store. And so that's been an interesting concept that we're really hoping to explore more is how many maps are there? When does the brain learn a new map? When is it worth the computational resources it takes for the brain to learn a new map? Does it only happen when there's some really important event, like a big reward, or can it happen just when you learn about new features of an environment? These are questions we don't have the answer to.

Nicholas Weiler:

And I want to bring this back to memory as well. It's interesting because I feel like we think about memories often as this very internal process. It's your story that you tell to yourself about yourself, but the connection with the navigation system really emphasizes how connected those internal stories are with our lived experience. Do you find that trying to understand this connection between memory and movement helps understand why some memories are so strong and so potent while others may fade pretty quickly?

Lisa Giocomo:

Yeah. I think the movement component hasn't been as widely explored, but it's definitely well known that there are features that can amplify our memories. So strong emotions, for example, or sometimes we use the terms in the animal research world of high valence. So a big Cheerio has a really high valence, something that has a high positive reward value. These things can definitely amplify memories.

The other thing that we know is that running seems to be associated with kind of an amplification of activities. So when animals are running through the world versus walking through the world, and we think that may relate to attention and general excitement. They're running towards a prey. They're running towards a food source, and so that can kind of amplify activity in a lot of these memory and navigation systems. But it's unclear still how much of that is related to the locomotor gate of running itself versus the attentive state of the animal. That's something that we're actually really trying to actively investigate is the degree to which attention plays a role or the goals or what the animal's trying to do versus the locomotor state itself.

Nicholas Weiler:

Yeah, I mean, it seems like the hippocampus is almost like a clearing house for bringing in lots of different aspects of experience, whether it's the space where you find yourself, the landmarks that you see, your sense of which direction you're going, but then also these emotional aspects, whether you're getting an exciting Cheerio or whether something frightening happened to you in a particular place. Again, it feels like how the objective reality of the outside world gets translated into the subjective story of our lives. Thinking about the future, thinking about the past and turning it into some sense of meaning. Is it too much to say that the hippocampus is playing a role in turning experience into meaning?

Lisa Giocomo:

I think in a way. I mean, one of the things that I think is so exciting about studying the hippocampus and the navigation system is that it really is an internal model of the external world. There's no sensory receptor for your sense of space. It's not like vision where we have the eye and the retina. It's not like touch where we have very specific touch receptors. It's not like taste where we have bitter, sour receptors. Our sense of space, our sense of memory really has to be constructed from all of those sensory features. It all has to be integrated into some kind of internal model inside our brain that then has this really big strong role in driving our behavior. It's such a fascinating system to study because it really is this internal model that the brain has to generate from the incredibly rich sensory environment that we exist in.

Nicholas Weiler:

Well, thank you so much for coming on the show. I wish we could talk more about this fascinating topic, but I think we're running short on time, but we'll have to have you back soon.

Lisa Giocomo:

That would be great. This was really fun.

Nicholas Weiler:

Thanks again to our guest, Lisa Giocomo. We'll include links for you to learn more about her work in the show notes and more information about memory palaces. It's just such a fascinating topic. It's probably something we all could use.

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From Our Neurons to Yours is produced by Michael Osborne at 14th Street Studios with production assistance from Morgan Honaker. Our logo is by Aimiee Garza. I'm Nicholas Weiler at Stanford's Wu Tsai Neurosciences Institute. See you next time. We'll see you next time.