Erasing Memories with Light

messing with memory. I thought you were going to say, it's one of my favorite things that pops up in my brain. It can be I don't know, are you guys. Do you guys ever have that issue where you are you are feeling really relaxed and content and you're you're feeling like things are really going well, and then your brain this whole this can't happen, and so pulls up a terrible memory of something you did where you made a complete jackass of yourself and then replays it. Yeah,

brains are jerks. It wouldn't be awesome to get rid of that memory so that we would no longer have that and when we're happy and content, we can just basque in the moment. Oh absolutely, and according to science fiction, this is easy peasy all the time, right continually. Wait, are we talking about about removing bad memories? Are adding good memories? Either one? Okay, so you have like inception, Sure, that's kind of that's more like than the dream world.

But that's related to memory, all right, fair enough, that can definitely involve Yeah, you're right that that is dreams. Yeah, that's getting mixed up there. But but total recall, Total recall. Now that's a classic film, and we're talking about the nineteen is the amazing, amazing science fiction film. I did not see the more recent one, but it looked slick and boring. I saw the original one in the theater. I remember all the stories coming out about how the

body count in that movie was astronomically high. Yeah, it's incredibly violent. Yeah, and it uh, of course has one of the best tour de force performances by Mr Schwarzenegger. You mean on the commentary track where he describes everything that's happening on the screen as it happens. That that also, I was thinking specifically in the context of the film itself, but it does in fact spill over into the meadow world around the film. Thank you, Thank you, Joe. Uh,

that was a direct quote. We want to make sure we reference that, but yeah, total recall. Of course, the the premise of the movie is that you have a character who he's kind of like going on a vacation, but in this in this case, he's having a vacation implanted in his mind. Yeah. The service they sell is they say, well, you know, it's cheaper than going on an actual vacation. We'll just give you memories that make

you feel like you had a vacation. And in this case, the memories were supposed to make him feel as if he were some sort of super spy who had traveled to Mars and been part of this major operation where uh it was you know, he was kind of the difference between life and death for the planet. But within the context of the film, it also opens up the possibility that he really is, in fact, this superspy and he just believes he's a normal guy because those memories

have been implanted. Yeah, So either way, whether you go with the story that he's a normal guy but believes he's a spy and everything else is playing out in his mind, or he really is a spy but he thought he was a normal dude because his memories had been supplanted by these these fake ones. We're talking about messing with memory. Uh, And this is not the only time we see this pop up in science fiction, certainly not. There was also Strange Days. Strange Days Out Where is

one of my favorite, incredibly disturbing films. I remember seeing that that movie and being very interested in the idea of this is this is just sort of a thing that is uh, sort of the often in that particular movie. But they have the super conducting quantum interference device or SQUID, and this allows you to record memories. So a person who has one of these devices can record memories that they are experiencing and then can essentially export those memories.

I mean they hold onto them themselves too, it's more like a copy. They can export a copy of those memories to someone else who can then experience those memories. In the context of the movie, it all ends up involving a robbery gone wrong, a bank has gone wrong, and then nefarious things unfold because of it. But yeah, there's another one where we're talking about letting someone experience the memory that they themselves have not actually formed personally

based on their own experience. There is eternal sunshine in the Spotless Mind. I remember I went and saw this in the theater knowing nothing about it, Like I hadn't even seen a trailer, and it was a great experience because I didn't know what was going to happen in the movie. It didn't have a clue, and when the

plot developed, spoil or alert that. It does eventually turn into a situation where there's a service in the movie that sells you the option of erasing memories, such as like the memory of an ex boyfriend or girlfriend right right, someone who you're no longer with, and you just want to wipe that from your brain entirely because it's just too painful, right like, like even the good memories, you want to get rid of them because now that you

no longer have that relationship, it's just a it's painful to even recollect. So that becomes the central premise of that film. And I mean, or at least that's the kind of the instigator for things that happened within the movie. Yeah, I'd say the central premise really is more of a question of, you know, should we do this? Do we really want to forget the things that we think we want to forget, and wouldn't we miss those memories if once we get to that situation, wouldn't we want them back?

And then, of course, another another central film in the concept of memory manipulation every bit is deep and loving is Men in Black with the neuralizer, the little the little a flash bang, a little flashy device makes you forget the last, you know, whatever, the last, however convenient it is to the plot many minutes that have just passed, so that the Men in Black can can convince everyone that it was just you know, swamp gas or an

electrical disturbance rather than aliens running amuck. Yeah, and actually less you forget. The best version of this plot device in films is in the Golden Globus film Superman. For where Superman, how is it possible that, no matter what the topic is, you somehow find a way of wrapping this back to Superman for a quest for peace? Well, you know, you've got to find peace somehow. Somebody's got to do it. It's not gonna be the President, it's not going to be the Russian. It's got to be Superman.

Produce your explanation and pray, make it improbable. Well, if you recall from the film, there's a scene where Superman basically reveals his identity to Lois Lane and then he wipes her memory, which it seems a abusive That also happens it that also happens in Superman too. Yeah, okay, okay, I totally forgot about it. Well, I've seen four more

recently than two. That's there's so much wrong. And what you just said Superman four, by the way, one of the memories I would love to earth, that would be that would be great. But then how would you remember the bad guy with his press on nails? And I wouldn't and it would make me a happier person. But we're getting that's fair. Yeah, we've have we been on

track yet. No. I think we've just talked about how how often people bring up the topic of I'd really love to create fake memories or get rid of real memories, or just strengthen memories I have because I know that there are there are conditions. There's just the process of aging where people have trouble remembering stuff, and I would

like to hold onto those memories for as long as possible. Yeah, So I guess the question within the realm of this podcast is is it possible we could actually do that technologically. So to answer that question, first, we have to explore what exactly is a memory. Now. On one level, of memory is a recollection of some stimuli that you encountered in the past. And that sounds vague, but it's because memory is a really big topic, right and we still

don't know exactly how it works all the time. The brain is a little bit mysterious, but but there is a physical process that we have more or less identified what's going on when we form and recall memories. So I'd say the brain is more than a little bit mysterious. Yeah, she's so. So we have a several regions of our brains right there. It's not just one big massive gray

matter with no differentiation between one part in the next. Uh. There is one region called the hippocampus, which is associated with forming long term memories. It's where hippopotamuses go to college. That's actually, yes, the hippocampus would be a big hippo on campus. I don't know that you're allowed to talk anymore. Uh. So this is part of the forebrain, and it's located inside the medial temporal lobe, and memories are made up

of neurons that communicate with each other through synapses. Now, synapses are those gaps between one neuron and other neurons, And of course neurons are the basic nerve cells in the brain exactly. So in the brain we have around between you know, eighty billion and a hundred billion neurons. A single neuron can have synapses that allow it to communicate with thousands of other neurons. It's not just a oh, it can communic yeah, or even a one to a

dozen thing. We're talking about the potential to uh, to communicate with hundreds or thousands of other cells. Again, depending upon the complexity of the brain we're looking at now with human brains, it's pretty darn complex. So how do neurons make memories? Do they what do they make new neurons or do they they form pathways of communication within the hippocampus. So I kind of imagine that this is oversimplifying, and and again this is base upon our current understanding

of memory. Keeping in mind that we don't have a yeah, we don't have a complete picture, but they form a pathway when you encounter us a stimuli that you need to remember something, let's say it's short term memory. They end up communicating with one another through electrochemical means. That's the way neurons communicate, and in short term memory, they just do a really quick and dirty, short electrochemical response that can be repeated a couple of times as necessary

for you to remember something while it's happening at the time. So, you know, short term memory where you're able to remember something for a couple of minutes, and then if you don't think about it, if you don't really try to commit it to memory, it's gone. That's what we're talking

about here. If you want to try and convert something into a long term memory where you're trying to really remember something, trying to get a concept down, like you're studying for a test and you're you're taking you know, you're reading this one passage, then resting for a while, and then reading the passage again and making sure you

understand it. This is where those that same communication pathway gets repeated, but now it's repeated with different proteins to kind of make it a more hesitate to use the word permanent, but a more stable pathway. All right, So you've got these neurons that are creating this same sort of pathway. Whenever you remember that thing that you've committed to memory, this pathway reforms, mostly because they're the actual process of remembering. It turns out that we have to

forge this pathway over and over again. Whenever we're filing the memory away, we're essentially recreating the memory that was created the first time. This is something that came out of studies that were started in the nineteen sixties really and then uh, you know, it didn't get widespread um acceptance within the brain research field until later. The common thought was that once you've created a long term memory,

you ended up consolidating it. That's what they called it was consolidation, and that your your memory was pretty much set like you would put it into long term memory, You're good to go. Uh. As it turns out that's not exactly what happens. You have this reconsolidation that happens where every time you are filing that memory away again so that you can recall it later, you are essentially

re encoding that memory. And that means that you could alter the memory through the re encoding process, so little details could change. This might be why if you hear someone tell the same story and you've known this person forever, you you think that's not the way that story goes. They totally left out this other part, or I don't ever remember hearing this thing they said this other time.

It might not be because they are trying to mislead you on purpose, but rather because they literally remember it differently exactly. The memory itself is different because the process of recalling a memory changes that memory. So as a as a related tangent, this should tell you that if the nature of memory is such that we re encode our memories every time we file them away, that tells you that relying upon memory for important stuff is not always a great idea and should perhaps not be relied

upon as heavily as it is. And say, like court cases, that's a great example. Yeah, so in a court case, you know, it's we often see that people put more importance on witness testimony than they do on other types of evidence. Not. Yeah, we're not. This is obviously a generalization.

It's not the case in every court case, but it's something that we see as a trend where people put the human element ends up having a greater impact on us than uh than either um, you know, things that we just have to uh conceptualize or just random pieces of information. The human element often seems to have a greater impact on us, which is unfortunate because memory is

not infallible. It doesn't mean that it's completely unreliable either, but it does mean that just by the very physical nature the way memories are formed, we cannot be completely certain that what we remember is exactly what has happened. Uh. It's a little worrisome or freeing, depending upon your point of view. I at this point wipe my hands of all responsibility, Like, Jonathan, you did this terrible thing. I have no memory of that, and I can be honest

or at least that's not the way I remember it. Um. But but even outside of this accidental changing of memories that happens, there has been a little bit of research right into how we can purposefully alter memory absolutely and a lot of this comes from some some studies that again started in the nineteen sixties, experiments that looked at

the hippocampus and the way that memories are formed. One of the things that were that we looked at was the fact that if you stimulate neurons in the hippocampus. You can make them better at communicating with each other. You can boost their ability to communicate, which means that you could help memories form more quickly, or you could

reinforce a memory, reinforcing that pathway. Uh. They used the electrical stimulation, and they called the process long term potential ation, also known LTP, which is pretty much how I'm going to say it from here on out, because potential ation I trip over it pretty frequently. So long term potential ation was suspected by some to play a really important role in encoding memories, but it wasn't necessarily again accepted

as a widespread concept for a while. They their brain researchers who said, well, it's obviously important, but I don't know that's the primary uh cause. And more importantly, we don't have enough direct evidence, right, because that's how science works. We can create a hypothesis, but until we test that hypothesis repeatedly and get the same result, we can't really draw a firm conclusion. That's the difference between hypothesis and theory.

And even theories can change, but they are more of a kind of consolidated uh, body of information that we understand about some aspect of the universe. And they're also different from the colloquial use of the word theory, in which you can say, well, I've got a theory that it's a demon, um, but so a singing demons right there, right exactly? Anyway, Yeah, sorry, back back to any sort of buffy quote and I'm going to jump all over it.

Rats at any rate. Rights. Yeah, so rats and mice, Uh, their experiments have been done with both with with LTP and forming of memories as well as erasing memories. But I'll get to that in a second. So how can you tell if a mouse or a rat is remembering something? You can't really sit down with the mouse or rats. Hey do you remember that one wheel of cheese? Man?

That was awesome? It doesn't really work. So one of the very common ways, here's where we get into the the part of the podcast that could very much upset some people, because we're talking about experimenting upon animals. Uh in the name of science. This is uh. One of the ways is conditioning them to fear a certain stimulus by following up that stimulus, well a little electric zap, so not enough to to really harm them enough to

enough for it to be a pain stimulus. So you're usually you're talking about like a certain pitch of sound and then you follow that up with a zap. Now, rats catch onto this really quickly from what I understand, you usually only have to do it once. And then they learned to associate the sound with getting zapped. And if you play the sound again, they freeze in anticipation

of the oncoming zap, So they build that memory very quickly. Um. But in order to try and test this LTP idea, what scientists would do is back in the nineties sixties, they started uh started doing this, and then they continue that into the eighties. They would establish something like the sound and the zapp, and then they would introduce some form of inhibitor that would inhibit LTP from taking place.

It would either be a drug or sometimes they would introduce a gene that would inhibit lt P, and then they would observe the rats and they saw that the rats would not be able to form a memory connecting the sound to getting zapped, or they would just essentially forget like they you could play the sound and they

wouldn't freeze, they didn't associate it anymore. They had forgotten that association, and that was some that was leaning more towards the evidence that LTP has this role in encoding memories, but still wasn't exactly conclusive. It was one of those things where says, all right, well, this is promising, let's continue research and seeing what else we can find. So that was the basis for that early LTP research. We'll

get back to that in just a minute. Right. What might have something to do with this is something called dendrid ex spines. And there's one study in particular that came out of NY you that was about sleep and how sleep strengthens memory. That has a lot to do with this, Okay, So, um, dendrid expines are these little protrusions between neurons and they facilitate the transfer of signals across synapses. Right. They grow in mice at least in the first few hours after the mice have learned a

new skill. So this is something that actually develops throughout the lifetime of the mouse as the mouse learns, you know, differential equations and right, you know how to do a Ronney dangerfield impression, that kind of thing exactly. Um, And and and they and they strengthen that memory of that skill UM, and these researchers found that these structures grow more during sleep. They trained two sets of mice at a task and then let one set sleep for seven hours and kept

the others awake for seven hours. The sleep deprived mice had less dendritic spine growth. Furthermore, they tracked which brain cells activated during the learning process, and those same brain cells reactivated while the mice were asleep, UM, specifically while they were in deep sleep, which is a slow wave sleep it's sometimes called, which is when the brain waves slowed down and dreaming and and or rapid eye movement stops. This.

This is really interesting for many reasons. This is some of the kind of current re search that's being done into exactly why this kind of long term memory formation happens. UM. In a separate study that was out of the Script's Research Institute, scientists UH did some of that inhibition thing that that you were talking about earlier. They inhibited the growth of dendrid expines a few days after training mice to associate methamphetamines with a few different site, touch and

scent clues. Later on, the mice lost all interest in those drug associated cues. While still maintaining longer held food reward memories. So they're they're hoping that this could lead to ways of selectively removing harmful memories like related to addiction or to PTSD or something like that, while still maintaining other other memories. Yeah, So in other words, you're not doing a full system wipe. You're wiping ones that

are causing uh, possible distress or problems in a person's life. Obviously, right now we're talking think about rodents, not people. And we'll we'll touch on that again in just a moment because and that's very important to remember rats brains and human brains in most cases. Yeah, but we've got some different stuff going on for most human beings. It's true

there may be exceptions at any rate moving on. So that's a great point, and we'll reiterate that when we get to a little bit further along in our podcast. We wanted to talk about another concept that's going to fold into this, optogenetics. Yeah, I thought this was really interesting.

So optogenetics is a fairly new tool in neuroscience, and it's when you genetically engineer cells, which in this case would be neurons brain cells, to become light sensitive, so you can either activate them or inhibit their activity with light with light waves, making it much easier to study and manipulate these cells. So it's a really simple on and off s which as opposed to the complex neurochemicals

and electrical signals that normally happen in a brain exactly. So, for one example, you can make neurons light sensitive by adding proteins called and I hope I'm pronouncing this right channel rhodopsins sounds good to me, abbreviated the two different kinds of them, c HR one and c HR two um, and you'll see these pop up sometimes in studies of optogenetics. These proteins occur naturally in algae, a certain type of algae that use light sensitive spots to help steer themselves

towards sunlight and water. They've got these flagella and they operate moving toward the light when the light strikes the spot. But once animal neurons are upgraded with for example c HR two, blue light triggers action potentials in those neurons. So in other words, you can target specific cells and turn them on whenever you want. And this is a really revolutionary research tool since it gives researchers unprecedented control and precision in studying how different cells in the brain work.

You can target really really really specific processes and single those out to see what they do. It's it's a little it's a little weird too, because it's almost like, hey, y'all, watch what happens when I push this button. So they said button, you're talking about regions of an animal's brain. So uh. And on a similar test, the University of California, San Diego had a research team that was looking into using optogenetics to further study the relationship between LTP and

UH encoding memories. And in this case, they got one of those genes that produces a light sense of protein. They put that into a virus. They then injected the virus into rat brains, which infected the neurons and transmitted this this gene to the neurons. So the neurons would end up having this light sense of protein in them

as well. So by again exposing the neurons to light the form of a fiber opt cable that was surgically implanted in the rat sprain, they could stimulate those neurons and thus stimulate LTP um or they could use a different set of pulses of light that would inhibit LTP. In fact, it it would stimulate what's called long term depression or lt D. It's kind of like the opposite of LTP. Lt D allows you to sort of um wipe away some of those pathways that would represent a memory.

And what they ended up doing was they targeted the pathway in the rats brains that connected the hearing uh the hearing processing center of the rats brain, with the part of the rats brain that deals with fear. And the reason for this was that they would stimulate the neurons in the rats brain so it would simulate a

the rat hearing a sound. They didn't play a sound, They just shine a light on that part of the rats brain, so the rat would remember sound exactly it had heard a sound, and followed that up, of course, with the requisite mild electric shock, meaning that when they would do that again shining the light on the rats brains, the rats would freeze just as if they had heard the sound, but they're reacting to a totally new type of stimulus. There's there's no actual physical sound being played,

So that was already kind of a breakthrough. Now, then they would use these pulses of light to induce lt D and effectively a race that association with the simulated sound and the electric shock. So when they would quote unquote play the stimulated sound again, the rats wouldn't react because they had forgotten. They no longer remembered that that

meant they were about to get zapped again. So this study is being looked at as yet another kind of strong evidence for the relationship between LTP and encoding memory. Uh not saying again that there aren't other lecular elements at play when you get to encoding memory, but that LTP does play a very important role, and that's really

why this research was covered so extensively. Um. Although I think a lot of the coverage was more about, hey, we can make rats remember and forget stuff, which is true, they actually did do it over and over essentially. One one article I said I read said they were playing yo yo with the rats memories, So, yeah, you remember, you forget, you remember, you forget um, like how Superman treats Lois Lane. Yeah, yeah, they were. They were giving

only in the only in those movies. Yeah, they were giving them the rats the kiss of forgetfulness and then reminding them, Hey, you know what that sound means, right, so I'm superman. Smooch, I'm Superman again. Smoot. The real problem was that Lois Lane kept forgetting other things like

they're when the piano lessons. All right, well, moving on to other things things to remember we you know, Lauren mentioned the potential of using this These the basic building blocks we're learning today in future therapies, and uh, and that is promising. It is something that would happen. If it does happen, it's going to happen years or decades in the future because memory is very complex, and again,

rhett brains and human brains aren't identical. And also the methods that we're talking about right now tend to be

fairly invasive or require some some pretty extreme measures. Yeah, it seems like you're either talking about genetic engineering, so you need to design this baby to be like this from the time it's a kid, or like introducing a virus to an adult, not to mention an optical fiber implanted in their brain, which would theoretically be connected to something that could produce the light necessary to shine on

the neurons. It's not something that is, it's not a noninvasive procedure in that case, right, right, Even some of the studies that I was talking about you would be discussing, you know, inducing or inducing a lack of protein growth in the brain after memories had been formed so that they could not form these dendrid expines. And this is this is dangerous stuff, as what we're saying, so I don't want to play around with it in a person.

That being said, it's possible that the stuff we're learning today will lead eventually to some very useful therapies, not just in helping treat people who have postramatic stress disorder or an addiction and they want to break, you know, they want to break those those neural pathways that are associated with forming a habit, which could in theory be really really useful, but also for things like strengthening memories for people who have a neurodegenerative disease like Alzheimer's where

they might have trouble, or someone who suffered a stroke, even uh, some people who might have trouble getting access to those this kind of information could help us perhaps in the future, rebuild these connections that were once thought to be completely lost. So people connect regain memories that they didn't even know they had. And that's the real trick about memory, right you can't remember what you don't

what you've already forgotten. It's you can't. Although you know, outside of UM degenerative brain disorders like that, there is a place for losing memories. It's actually an important part of the of the brain process. I argue this all the time with my wife and she does not believe me. Well, okay, so do you still remember Superman? For Unfortunately, that one has stayed with me and every time I bring it up,

I'm strengthening that connection. Well, there's another connection that's happening right now that's associated with you, Joe, and I think you might want to tread lightly before you continue done this path. I'm talking about some specific research that was done I was done at the University of British Columbia that indicates that when connections between neurons are too strong that they call it sticky UM. That means that the

new things are difficult to learn. UM, that it becomes more difficult for us to modulate our behavior and and adapt to changes. Stuff like that. That's really interesting. I also think that you know, we didn't really cover this in our notes, but it kind of leads into that also the idea of uh, of facilitating education. You know the fact that memory and and and learning are very

closely connected. Things like can you imagine being able to use sort of these techniques to to strengthen our brain when learning something like a new language and uh, something that is very well, something that is easier for younger people to do than it is for old fogies like me, who it's not that I can't learn a new language, it's just that it's gonna take me more effort to do something that a younger person will pick up much

more quickly. UM. I could see this kind of research eventually leading to techniques that would allow us to facilitate learning in different stages of our life, so that it's one of those you know, we can regain that plasticity that we have when we're younger and really uh and apply that to whatever it is we're interested in when

we're older. Again, this is stuff that we're talking about years and years and decades into the future, because there's so much about the brain we don't understand and that we don't even know we don't know that it's going to take some time before we can even address this in a remotely experimental way, much less in a widespread like you know you go to the learning store and

get yourself some French lessons. So if you guys out there who have been listening to this podcast think, hey, I always wanted to ask this one question, but I keep forgetting to do it. Now is the time to remember. And if you do remember what it was that you wanted to ask, but you don't remember how to contact us, I'll remind you Twitter, Facebook, Google Plus, all great avenues to explore. Use the handle FW thinking to find us. And we look forward to hearing from you, and we'll

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