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Question: What is the relationship between memory and fear? 

Joseph LeDoux: So, whenever we have a memory about some experience, it turns out that there are probably a lot of different systems in the brain that are being activated. As scientists, we sometimes talk about "memory systems," but I sort of think that that’s a misnomer. Because if you think about what memory is, it’s really plasticity in the nervous system. It’s the ability of neurons in the brain to change and neurons in every part of the brain that we’ve looked at have this capability of changing, of become plastic when their experiences change. 

Now, from the point of view of the neuron, an experience is the arrival of neurotransmitters being released by another neuron. So, what that does is it changes the way that neuron responds. And across many such events like that in the brain, a memory is formed, or multiple memories are formed. So, it’s really inappropriate to talk about memory systems because almost every system in the brain forms memories. So, what we like to think about instead, or the way I like to think about it is that memory is a feature of neurons rather than a function of brain systems. So, as information goes through a brain system, if that information is significant, it will form a lasting trace as a result of the release of the transmitter and the other things that are going on at that same time will form a trace, a connection between the active neurons and that will stay in the brain in the form of what we then experience as memory later. 

Now, let’s take a situation where you’re driving down the road and you have an accident. You hit your head on the steering wheel and you hit it really hard and the horn gets stuck on and so you hear this loud and annoying noise while you’re bleeding, in pain, it’s really awful and terrible. And then a few days later, you hear the sound of a horn. So, that sound will go to various parts of your brain simultaneously. When it goes to a part of the brain called the hippocampus, it will remind you of the situation that you’re in that you were driving, that you had an accident that you were with John and Peg. But it won’t have the emotional impact unless it also goes to a different part of the brain called the amygdala, which instead of reminding you of the details of the event, will trigger emotional responses in your brain and body, and the ones in the body will feed back to the brain, and all of that activity in the brain will give rise to what we call the emotion. 

So, back to the fear example, the sound of the horn goes to one part of the brain, the amygdala and gives rise to the emotional response into the other part of the brain, the hippocampus, and gives rise to the cognitive representation. So, we call the hippocampal memory, a memory about the emotion, whereas the amygdala memory we call the emotional memory itself. Now these two things happen simultaneously, the amygdala memory is triggered unconsciously, it don’t have to be aware of the stimulus in order for that to be triggered. Hippocampal memory is probably triggered unconsciously as well, but you become aware of the memory when it’s triggered because that’s what a hippocampal memory does, it creates a representation of the conscious experience. 

But that conscious representation now is going to be amplified by the emotional arousal that's taking place, it’s going to create a new emotional memory, or new memory about emotion that’s going to have that kind of emotional stamp on it. So, it’s the interaction between cognitive systems and emotion systems in the brain that create what’s called sometimes, flashbulb memories, which are very vivid strong memories of a particular experience. 

Or everyone my age remembers the assignation of John Kennedy in the ‘60’s; remember where we were, what we were doing, and all those gory details. Now, it used to be thought that these flashbulb memories were more accurate than other memories. But new research by Liz Phelps, my colleague at NYU and other researchers, that study humans, have shown that these flashbulb memories are not more accurate, they’re just more vivid. So, the accuracy is kind of suspect and one of the consequences, or one of the implications of that is that, memories are constructed, or reconstructed when they’re retrieved. And at that point of retrieval, the memory has the opportunity to be changed. And that’s one of the main topics we’ve been working on lately is how memory has changed when it’s retrieved. 

Question: How does memory change when it is retrieved? 

Joseph LeDoux: So, a good example of the way memory changes during the retrieval process is a situation where someone goes to court to testify about a crime that they witnessed. And on the day of the crime, you know, they gave their summary of what happened to the police so there’s a police record at the time. And then when they go into the court, they talk about something completely different, which it turns out happens to match what they read about in the newspaper. And so when they read the newspaper, what they did was the updated their memory about the experience and then in the future, when you retrieve that memory, it’s hard to distinguish, you know, what actually happened and what you’ve incorporated since through other kinds of experiences. 

And this is now well-known phenomenon that each time a memory is taken out, the opportunity is there for it to be changed. And normally this is an updating process and it’s a useful thing. If you meet somebody at a party and so it’s a nice guy, but then you find out he’s an axe murderer or something like that, you have to immediately change your memory of that person, so you’ve updated it. There are other ways the memory gets updated as well; let’s go back to the example of fear conditioning in the rats. So, we conditioned a rat to be afraid of the tone. So, the next day, he hears the tone and he freezes, because that’s how rats express their fear of the stimulus. But immediately after presenting that tone, we give the rat a certain kind of drug, which I’ll explain later, and we test the rat the next day, the memory is no longer present—or at least can’t be accessed. So, what’s going on? 

Well, it’s been known for a long time that memory formation or memory consolidation requires the synthesis of new proteins in the parts of the brain that are forming the memory. So, other researchers discovered then that memory... that if you block protein synthesis after retrieval you can also disrupt the stability of the memory later. But that idea kind of got lost in the late ’60’s and didn’t stick around. What stuck around was the idea that memories are consolidated and once they are consolidated, each time that you take it out, you take out that same trace over and over again. 

So, the new research which my lab helped sort of rejuvenate in the year 2000, was about manipulating the memory after the rat experiences the retrieval process. So, we give the rat the tone, and then we block protein synthesis after retrieval, rather than after learning. And when we do that, again, the memory is eliminated just as well after retrieval as it it’s prevented from being acquired after learning if you block protein synthesis. 

So, the unique feature of our experiment was, we were able to do this in the side of the brain where the memory is being formed and stored, which in the case of fear conditioning memory is the amygdala. So, because we did all of the basic work or figuring out all of those circuits, we could go in and put a tiny amount of a protein synthesis inhibitor in the amygdala. And that’s important because you can also do this experiment by giving the protein synthesis inhibitor systemically to the whole body, like if you take a pill, that goes into your body and reaches your brain and does all the stuff, but it’s going everywhere and that’s why many drugs have side effects. So, if you take an anti-anxiety drug, it not only relieves anxiety but it would make you sleepy, it might alter your sex drive, blah, blah, blah. 

So, what we’re doing here is avoiding one of the bad consequences of protein synthesis inhibitors, which is that it makes you nauseous and sick and so forth if you take it systemically. And it is pretty toxic, so you would never give a drug like that to a human. This is only something you can do in an animal experiment. So, the protein synthesis inhibitor in our studies was put directly in the amygdala and we avoid all of those side effects and negative consequences since it’s a tiny amount and it doesn’t affect the rest of the body. 

So, when we do that, the rats the next day don’t freeze to the tone. They don’t remember that the tone is now dangerous. So this is triggered a whole wave of research now on the possibility of using this as a treatment for Post Traumatic Stress Disorder because theoretically we can have the people come in, remember their trauma, give them a pill and the next time the cues about the trauma come along, they won’t have the emotional response to it. 

Question: Have you learned anything by fear? 

Joseph LeDoux: Well, when I was a kid, I was really afraid of snakes. I grew up in Louisiana where there are tons of really awful snakes called water moccasins and we used to go water skiing all the time. And every water skiing spot has this legend that the person who falls in the water and says, “Oh, I’m trapped in some barbed wire or something,” and they pull him out and he’s covered with tons of baby water moccasins just sucking away on him. So, I was a really good water skier because I learned to ski without getting wet. So I would stand on the pier and the boat would take off, I’d just jump in on the skis and ski around and then just ski back up on the land. 

But the way I acquired this fear of snakes, I think, is we went craw fishing once at this old bayou and there were... it was a hot afternoon and the bayou had... and I remember this very vividly, this is my flashbulb memory, who knows if it’s accurate, but it’s very vivid. So, it has this sloping side of the bank of the bayou and there were like, it seemed, thousands of snakes on both sides, just kind of basking in the sun. And I just found it a really terrifying, vivid memory. But, you now, I really don’t worry about snakes anymore. When I was younger, if I turned to a picture of a snake in a magazine it would freak me out, but it doesn’t really bother me. 

Question: How does a stimulus provoke a fight-or-flight response in the brain? 

Joseph LeDoux: Well so, whenever you encounter some sudden danger out there in the world, the information from that stimulus, let’s say it’s a snake on the path would go into your brain through your visual system, if it’s a visual stimulus. And then will rise through the visual system through the standard pathways. So, every sensory system has this very well organized set of circuits that ultimately leads to a stop in the part of the brain called the thalamus en route to reaching the sensory cortex. So each sensory system has an area in the cortex. The cortex is that wrinkled part of the brain that you see whenever you see a picture of the brain. And that’s where we have our perceptions and thoughts and all of that. 

So, in order to have a visual perception, information has to be transmitted from the eye, from the retina, through the optic nerve, into the visual thalamus, and from the visual thalamus to the visual cortex, where the processing continues and you can ultimately have the perception. So, the visual cortex connects directly with the amygdala, and so that one route by which the information can get in; retina, thalamus, cortex, amygdala. But one of the first things that I discovered when I started studying fear was that that pathway, the usual pathway that we think about for sensory processing was not the way that fear was elicited, or not the only way. 

What we found was that if the cortical pathway was blocked completely; rats could still form a memory about a sound. We were studying sounds and shocks. But we’ve also done it with a visual stimulus. So, what we found was the sound had to go up to the level of the thalamus, but then it didn’t need to go to the auditory cortex or the visual cortex as if it were a visual stimulus. Instead, it made an exit from the sensory system and went directly into the amygdala, below the level of the cortex. That was really important because we generally think that the cortex is required for any kind of conscious experience. So, this is a way that information was being sent through the brain and triggering emotions unconsciously. So, the psychoanalysts love this because it vindicated the idea that you could have this unconscious fear that the cortex has no understanding of. 

So, the idea was elaborated a bit into this concept where it’s possible that the cortical and the thalamic inputs to the amygdala could become dissociated in people for one reason or another such that the stimulated, or triggering amygdala from the thalamus wouldn’t necessarily match those that the cortex is attending to. So, in order, again to consciously attend to the stimulus, you need the cortex. 

So, let’s say we were having lunch one day and there’s a red-and-white checkered table cloth, and we have this argument. And the next day I see somebody coming down the street and I say, I have this gut feeling about this guy, he’s an SOB and I don’t like him. And maybe what’s going on there is that he’s got a red-and-white checkered necktie on. Consciously, I’m saying it’s my gut feeling because I don’t like the way he looks, but what’s happened is that the necktie has triggered the activation of the amygdala through the thalamus, the so-called low road, triggered a fear response In me, which I now consciously interpret as this gut feeling about not liking the guy. But in fact, it’s being triggered by external stimuli that I’m not processing consciously. 

So, this is important because a lot of people have fears and phobias and anxieties about things they don’t understand. They don’t know why they’re afraid or anxious on a particular time. It may be through various kinds of experiences, the low road gets potentiated in a way that it’s activating fears and phobias outside of conscious awareness and that doesn’t make sense in terms of what the conscious brain is looking at in the world, or hearing in the world because they’ve been separately parsed out. 

So, the subcortical pathway... we’ve been able to time all of this very precisely in the rat brain and, in order for a sound to get to the amygdala from the sub cortical pathway takes about 10 or 12 milliseconds. So, take a second and divide into 1,000 parts, and after 12 of those little parts, the amygdala was already getting the sound. Consciously, for you to be consciously aware of the stimulus, it takes 250-300 milliseconds. So, the amygdala is being triggered much, much faster than consciousness is processing. 

So, the brain ticks in milliseconds, the neurons process information on the level of milliseconds, but the mind is processing things on the order of seconds and half-seconds here. So, if you have a fear response that is being triggered very rapidly like that, consciously you’re going to be interpreting what’s going on, but it’s not going to necessarily match what’s really going on. 

Question: Why did you first start playing music? 

Joseph LeDoux: Well, I think in the early ‘60s, everyone had a folk guitar. I grew up in south Louisiana where music is very big, Cajun music and so forth. Of course, I wanted nothing to do with that when I was growing up, but the folk revolution had taken place and so everybody had folk guitars, they were learning Simon and Garfunkel. I had just got a Facebook message from someone I had went to high school with asking me if I remembered the day we played at the school auditorium where we played “Sounds of Silence” and I did remember that because I could never play that B flat cord with my young hands at that point. 

So, yeah, I started then and then I was taking a bath and had a transistor radio one night and “I Saw Her Standing There” came on the radio and that kind of like changed my life, the “Beatles” had come to town and so then we threw away our acoustics and go electric guitars, formed a band and started playing around town. We had a couple of bands. There was my band and then this other group. We kind of tended more towards the more bluesy “Rolling Stones” kind of stuff and the other band was actually better and they could play all the “Beatles” songs and sing them. We couldn’t actually achieve that, so we said we’re going to be more authentic. We’re going to be more bluesy and these other guys can be just “Beatles” copies, but they were much better. 

I’m actually in touch with a couple of the guys from the other band, again through Facebook and things. So, yeah, I always loved music. I became a disc jockey in the local town in this Louisiana, I think my senior year in high school and had a radio show and I think Friday nights and Sunday morning something like that. And then went off to college and had one little brief band thing there, which is kind of prophetic in the sense that we called ourselves “Cerebellum and the Medullas.” At that point I was studying marketing and business and I had no inclination of being a scientist. It wasn’t like I was into that whole brain thing at that point, but at some point I did switch gears. I got a masters in marketing and while I was doing that, I became interesting in psychology and started studying psychology and took a course with a guy studying the brain, and just threw all the other stuff away. I wasn’t that into the marketing anyway. And the brain just seemed like an amazing thing to study, so I said, "That’s what I want to do."

But you know, for the rest of most of my adult life, I didn’t play guitar. I had it around but I didn’t do much with it. And at some point I just picked it up again and started taking lessons and started getting more into it. And started picking around with Tyler Volk, who is a biology professor at NYU, and we used to just get together and jam and you know, dream about having a band someday. 

And then in the fall of 2006, I got an invitation to give a lecture at the Secret Science Club in Brooklyn, it was held in the basement of the Union Hall in Park Slope, a tiny little room. So, I gave the lecture and they said, well we’ll get some entertainment. And I said, well I’ll bring the entertainment. And so Tyler and I decided to go off and try this out and so we recruited Daniela Shiller who is the post-doc and we knew she played drums, and she had played with us on a couple of occasions at parties and stuff. And she happened to have a research assistant named, Nina Curley, who played bass. So, you know, we practiced a couple of times, headed out to Brooklyn, and Amygdaloids were born at that moment. 

Question: What is your newest album about? 

Joseph LeDoux: Both of our albums, the songs are about research. They’re all mind, brain, mental disorder related songs. So, the first album, the kind of signature song and kind of the band theme song is “All in a Nut,” which is a tribute to the amygdala is the almond in your brain. Amygdala means almond, it’s a Greek word for almond. So, that was one. We wrote a song called, “An Emotional Brain,” which is a takeoff on “The Emotional Brain,” which is all about different kind of mental disorders and facial expressions of emotions, things like that. We had this pretty good song called “My Body Problem,” which is a tribute to Descartes. All our songs are love songs really, so the “Mind Body Problem” is “My body wants you so, but my brain says, no.” “Inside of Me,” is another Descartesian song where it’s about you can’t see inside of me, it’s a place I can only be because, you know, Descartes' view of the mind, only you can know your own mind, and you can’t know the mind of anyone else directly. And we also had a song called “Memory Pill,” which is about erasing memory through drugs and so forth, and that is related to all of this research I was just talking about. So, then we did that in sort of a vanity press kind of album, at least we paid for it ourselves, and it came out really well. 

And then we met some folks who were interested in using music as a therapeutic device, and they came across me and my research and music and they decided that they wanted to do a CD with the band and their company is called Knock Out Noise, they’re a small record production company. And so we talked about concept and so forth and over time, we came to terms and they produced the second CD. It took a couple of years to kind of do the whole thing. It was ready much earlier than that, but we did a lot of post-production cleaning up and stuff, and added some songs at the last minute that we didn’t have originally on it. And the original idea for that CD was going to be to call it “Brain Storm,” but then we decided to change it to something else that had a more of serious scientific edge to it, so it’s called “Theory of my Mind.” It’s based on theory of mind idea, which is that in order for us to have social interactions, we have to have a theory of what’s in the other person’s mind so we can anticipate their behavior on the basis of what we know about them and their emotional responses and so forth. 

And I was in Cambridge, England on sabbatical last spring where Simon Baron Cohen is. He’s the main guy of “Theory of Mind in Autism.” And so I actually recorded Simon on bass and one of his colleagues, Bishma on tabla, and layered that on top of the recordings that we have of the “Theory of My Mind,” it sounds really good. So, it’s “Theory of My Mind” which is like in a love song, "You don’t understand me, you don’t have a theory of my mind," and blah, blah, blah. 

So that’s the title song of the CD. We’re really fortunate on this CD to have Rosanne Cash singing two songs with me as my backup vocalist, not bad. And she sings on “Mind over Matter,” which is my favorite song and everyone who hears it says, if we have a hit, this is the one that would be a hit. It’s a really nice kind of airy song and that’s the one I’ll sing for you in a few minutes. 

It’s about love and loss and longing for someone who’s not there but you kind of use your mind to conquer the space and time that separates you from that person. Another song on the CD that Rosanne sings on is, it’s funny that she sings on it because as I was writing it and kind of getting the music out for it, I was sort of in my mind imagining, channeling Johnny Cash, and it’s a song about a guy who’s in prison on death row. And the reason I wrote this song is, I’ve gotten a number of letters and emails from people on death row asking for help in their defense because something called the Amygdala Defense has emerged, which is: "I didn’t do it, my amygdala did." And unfortunately for them, I don’t think that the amygdala can actually commit a crime. I think it’s possible for crimes to be committed or complex behaviors to be controlled unconsciously, but it’s not the amygdala that’s doing it. The amygdala is responding to sudden threats and producing automatic rapid responses, mostly innate hardwired response. So, I don’t think my expertise can really help them. But I do think that there is an argument can be made that a person can commit a crime of passion that’s outside of their control because either they’re under tremendous stress or the factors that cause them to do things that they wouldn’t ordinarily do. 

Now, the bottom line problem is, how do you prove that in this particular case, that’s what went on, or is that just a convenient thing to say after the fact. So, that’s why I try not to get involved in legal things because I don’t’ think I could say one way or another in this particular case, or in any case, that this is definitely what was going on. But I do think the court should take that into account and be kind of hip to the fact that the brain can do things unconsciously and should weight that as part of the evidence. 

So in “Crime of Passion,” the guy catches his wife with someone else and kills the other guy and so he’s kind of singing to the wife from prison saying, you know, "You’re not worth what I’m going through." And so it’s not a, "Oh I love you so much and how could you do this to me?" It’s about, "Why did I do this, you’re not worth it."

Question: How is your music related to your work as a neuroscientist? 

Joseph LeDoux: The reason I’m doing what I’m doing now is I’m trying to integrate the science and the music into a kind of seamless whole, because music is such a powerful communicator. And I’ve written books like, “The Emotional Brain” and “Synaptic Self” that have been translated into dozens of languages each and they’ve been really good sellers, but I think we can reach a different audience with music. So, I’m not saying I can convey as much in a song as I can in a book, or even a book chapter, but I might be able to trigger an interesting spark or idea in someone that might not be prone to pick up a book. So, well, "What is the mind/body problem?” or "How do emotions come out of the brain?" or "Can a crime of passion really be committed?" And to pick up a book or do some research on the Internet and it’s kind of like raising awareness of the brain through music. 

And so I do think that music is just really powerful, but personally, I’ve never been inclined to study it, I just haven’t been – It’s not what I’ve been doing and there are enough people that are doing that pretty well that I leave that to them. And so I just use the music as a vehicle or tool to convey the scientific information, although I’m not studying it myself. 

Question: Play a song for us. 

Joseph LeDoux: This is “Mind over Matter,” by the Amygdaloids, on our new CD, “Theory of my Mind.” 

Mind over matter, something I’m trying to do 
It’s just a little physics that keeps me apart from you. 

Mind over matter, something I’m trying to do 
Break down the space and time, to be together with you. 

I’m trying to will you here, find you wherever you are 
Locate your body, your soul, pull you in from afar 

Are you still in my time, or have you slipped away? 
Have you gone forward to die, living in another day? 

Well where am I to be? This isn’t time to move it on you see 
In the air violently, we’re in a place heavenly 

Wherever you are now, I’ll use my mind to find 
Know now that space or time, keeping me in line 

Mind over matter, it’s something I’m trying to do 
Just a little physics, that keeps me apart from you. 

Mind over matter, it’s something I trying to do 
Break down space and time, to be together with you 

Be together with you, 
Be together with you, 
Be together with you.

Recorded on May 5, 2010
Interviewed by Austin Allen
 

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