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Speaker A: Welcome to the Huberman Lab podcast, where we discuss science and science based tools for everyday life. |
Speaker B: I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today, my guest is Doctor David Anderson. Doctor Anderson is a professor of biology at the California Institute of Technology, often commonly referred to as Caltech University. Doctor Andersen's researc... |
Speaker A: I cannot recommend the book highly enough. |
Speaker B: Again, the title is the nature of the beast, how emotions guide us. Today's discussion also ventures into topics such as mental health and mental illness, and some of the exciting discoveries that have been made by Doctor Anderson's laboratory and other laboratories. Identifying specific peptides, that is, s... |
Speaker A: Indeed, he is a member of the. |
Speaker B: National Academy of Sciences and a Howard Hughes Medical Institute investigator. I've mentioned the HHMI once or twice before when we've had other HHMI guests on this podcast. But for those of you that are not familiar, the Howard Hughes Medical Institute funds a small number of investigators doing particula... |
Speaker A: In keeping with that theme, I'd like. |
Speaker B: To thank the sponsors of today's podcast. Our first sponsor is element. Element is an electrolyte drink with everything. |
Speaker A: You need and nothing you don't. |
Speaker B: That means plenty of salt, magnesium, and potassium, the so called electrolytes, and no sugar. Now, salt, magnesium, and potassium are critical to the function of all the cells in your body, in particular to the. |
Speaker A: Function of your nerve cells, also called neurons. |
Speaker B: In fact, in order for your neurons to function properly, all three electrolytes need to be present in the proper ratios. And we now know that even slight reductions in electrolyte concentrations or dehydration of the body can lead to deficits in cognitive and physical performance. Element contains a science ... |
Speaker A: Sure I have enough electrolytes. |
Speaker B: And while I do any kind of physical training and after physical training as. |
Speaker A: Well, especially if I've been sweating a. |
Speaker B: Lot, if you'd like to try element, you can go to drinkelement. That's lMnt.com huberman to claim a free element sample pack with your purchase. Again, that's drinkelementlmnt.com hubermandhe. Today's episode is also brought to us by waking up. Waking up is a meditation app that includes hundreds of meditatio... |
Speaker A: So I gave the waking up app a try and I too found it. |
Speaker B: To be extremely useful because sometimes I only have a few minutes to meditate, other times I have longer to meditate. And indeed, I love the fact that I can explore different types of meditation to bring about different levels of understanding about consciousness, but also to place my brain and body into lo... |
Speaker A: David, great to be here and great to finally sit down and chat with you. |
Speaker C: Great to be here too. Thank you so much. |
Speaker A: Yeah, I have a ton of questions, but I want to start with something fairly basic. But that, I'm aware, is a pretty vast landscape, and that's the difference between emotions and states. If indeed there is a difference and how we should think about emotions, what are they? They have all these names, happiness... |
Speaker C: That's great. First, the short answer to your question is that I see emotions as a type of internal state in the sense that arousal is also a type of internal state. Motivation is a type of internal state. Sleep is a type of internal state. And the simplest way I think of internal states is that, as you've s... |
Speaker A: What are the different components of a state? You mentioned arousal as a key component. What are some of the other features of states that represent this, as you so beautifully put in your book, that represent below the tip of the iceberg? |
Speaker C: Right. Right. So you can break states up into different facets, or people would call them dimensions. And so there have been people who have thought of emotions as having just really two dimensions. An arousal dimension. How intense is it? And also a valence dimension, which is, is it positive or negative, g... |
Speaker A: Now, you mentioned arousal a few times, and you mentioned valence. Realizing that there are these other aspects of states, I'd like to just talk about arousal a little bit more and valence, because at a very basic level, it seems to me that arousal, we can be very alert and pissed off, stressed, worried. We ... |
Speaker C: I would be reluctant to say that it's a chemical flip. I would say it's more likely to be a circuit flip, different circuits being engaged. And it might be that a given neurochemical, even dopamine, is involved in both positively valence arousal and negatively valence arousal. That's why people think about t... |
Speaker A: Yeah, it's a super interesting idea, because I always thought of arousal as along a continuum. You can either be in a panic attack at the one end of the extreme, or you can be in a coma and then somewhere in the middle, you're alert and calm. But then this issue of valence really, as you say, presents this o... |
Speaker C: Yeah, this is a great question, and it's a large area. I would say that, first of all, the word aggression, in my mind, refers more to a description of behavior than it does to an internal state. Aggression could reflect an internal state that we would call anger in humans, or could reflect fear, or it could... |
Speaker A: They like it. |
Speaker C: They like it. Male mice will learn to poke their nose or press a bar to get the opportunity to beat up a subordinate male mouse. And in more recent experiments, if you activate those neurons and the mouse has a chance to be in one of two compartments in a box, they will gravitate towards the compartment wher... |
Speaker A: Anatomists are so creative, or the nucleus. |
Speaker C: Ambiguous, or the zona incerta. These are places that no one can think of what they are anyhow, that might be a final common pathway for predatory aggression and offensive and defensive aggression. But it can be really hard to tell just from looking at a mouse fight whether it's engaged in offensive or defen... |
Speaker A: I've seen some nature specials where, in a very barbaric way, at least to me, it seems like hyenas will try and go after the reproductive axis, they'll go after testicles and penis, and they basically want to it seems they want to limit future breeding potential or create pain. Or create pain or both. Yeah, ... |
Speaker C: Yeah, I think that is a very profound question, and I've wondered about that a lot. If you think from an evolutionary perspective, it might have been the case that defensive behaviors and fear arose before offensive aggression, because animals first and foremost have to defend themselves from predation by ot... |
Speaker A: Mixed together in VMH as well, controlling body wide metabolism. |
Speaker C: Yeah, there are neurons there that respond to glucose. When glucose goes up in your bloodstream, they're activated. And VMH has a whole history in the field of obesity, because if you destroy it in a rat, you get a fat rat. So the way most of the world thinks about VMH is they think about, oh, that's the thi... |
Speaker A: One of the things that we will do is link to the incredible videos of these mice that have selective stimulation of neurons in the VMH dius and the other studies that you've done. Whenever I teach, I show those videos at some point with the caveats and warnings that are required when one is about to see a vi... |
Speaker C: Yeah. So really important question. I think one way that is helpful, at least for me to break this question apart and think about it, is to distinguish homeostatic behaviors, that is, need based behaviors, where the pressure is built up because of a need. Like, I'm hungry, I need to eat, I'm thirsty, I need ... |
Speaker B: Or Twitter. |
Speaker C: Yeah, Twitter. |
Speaker A: Twitter seems to. I'm sort of half joking because Twitter seems to draw a reasonably sized crowd of people that are there for combat of some sort. Even though the total intellectual power of any of their comments is about that of a cap gun, they seem to really like to fire off that cap gun. But I agree. |
Speaker B: I'd like to take a quick break and acknowledge one of our sponsors, athletic greens. Athletic greens, now called ag one, is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs. I've been taking athletic greens since 2012, so I'm delighted that they're sponsoring the podca... |
Speaker C: Yeah. So you can think of this accumulated hydraulic pressure either being based on something that you were deprived of, creating an accumulating need, or something that you want to do, building up a, a driver of pressure to do that. And the natural way to think about that, at least for me, is as a gradual i... |
Speaker A: Fascinating. And I should mention people Doctor Anderson mentioned. Lindsey Lindsay is a former graduate student of mine that's now a postdoc in David's lab. And I haven't caught up with her recently to hear about these experiments, but they sound fascinating. Would love to spend some time on this issue of w... |
Speaker C: Right. That is the central question. I can say, at least with respect to the fear neurons that sit on top of the aggression neurons. We know that when those neurons are activated optogenetically, in the same way we would activate the aggression neurons, that there's clearly an arousal process that's occurrin... |
Speaker A: I want to talk more about mating behavior, but as a segue to that, as we're talking about aggression and mating behavior, I think hormones, and whenever there's an opportunity on this podcast to shatter a common myth, I grab it. One of the common myths that's out there, and I think that persists, is that tes... |
Speaker C: Yeah, that's a really important question. So, when we finally identified the neurons in VMH that control aggression with a molecular marker, we found out that that marker was the estrogen receptor. So that might strike you as a little strange. Why should aggression promoting neurons in male mice be labeled w... |
Speaker A: Fascinating. So estrogen is doing many more things than I think most people believe, and testosterone is doing maybe different and fewer things in some cases and more in others. I've known some aggressive females over the time I've been alive. What's involved in female aggression that's unique from the pathw... |
Speaker C: Great question. We and other labs have studied this in both mice and also in fruit flies. So one thing in mice that distinguishes aggression in females from males is that male mice are pretty much ready to fight at the drop of a hat. Female mice only fight when they are nurturing and nursing their pups after... |
Speaker A: I'm fixated on this transition from the virgin female mouse to the maternal female mouse. I have a couple questions about whether or not, for instance, the transition is governed by the presence of pups. So, for instance, if you take a virgin female, she'll mate with a male. Once she's had pups, she'll try a... |
Speaker C: Equally towards females and male intruders. |
Speaker A: Does that require the presence of her pups? Meaning, if you were to take those pups and give them to another mother, does she revert to the more virgin like behavior? Is it related to? Is it triggered by lactation? Or could it actually be triggered by the mating behavior itself? Cause it's possible for the v... |
Speaker C: Right. Those are all great questions, and we don't know the answer to most of them. What I can say is that a nursing mother doesn't have to have her pups with her in the cage in order to attack an intruder male or an intruder female. She is just in a state of brain that makes her aggressive to any intruder. ... |
Speaker A: I don't want to anthropomorphize, but. Well, I'll just ask the question. So the other day I was watching ferrets mate. They're mustelids and they're mating behavior. I guess I didn't say why I was watching this doesn't matter. It simply doesn't matter. But if one observes the mating behaviors of different an... |
Speaker C: Right. Great, great questions. I can't really speak to the issue of whether this is species specific because I'm not a naturalist or a zoologist. I've seen, like you have in the wild, for example, lions, when they mate, I've seen them in Africa. There's often a biting component of that as well. One of the th... |
Speaker A: I'm sure people's minds are running wild with all this. I'll just use this as an opportunity to raise something I've wondered about for far too long, which is, I have a friend who's a psychiatrist who works on the treatment of fetishes. This is not a psychiatrist that I was treated by. I'll just point that o... |
Speaker C: Right? I would agree. I think one way of looking at fetishes from a neurobiological standpoint is that they represent a kind of appetitive conditioning, where something that is natively aversive or disgusting by being repeatedly paired with a rewarding experience, changes its valence, its sign, so that now i... |
Speaker A: Definitely an area that I think, well, human neuroscience in general needs a lot of tools in terms of how to probe and manipulate neural circuitry. I'd love to turn to this area that you mentioned, the medial preoptic area. I'm fascinated by it, because just as within the VMH, you have these neurons for mati... |
Speaker C: I don't know what the relationship is between temperature and mating neurons in the preoptic area. I suspect that they are different populations of neurons, because it's become pretty clear that the preoptic area has many different subsets of neurons that are specifically active during different behaviors, e... |
Speaker A: Wait, wait. So I think I've heard this before, but I just want to make sure that people get this. I want to make sure I get this. So you're telling me within medial preoptic area, there are specific neurons that if you simulate them, will make males thrust as if they're mating? |
Speaker C: No. So this is not based on stimulation experiments, it's based on imaging experiments. |
Speaker A: Right. |
Speaker C: Now that we see, when we look in the preoptic area at what neurons are active during different phases of aggression, we see that there are different neurons that are active during sniffing, mounting, thrusting, and ejaculation, and they become repeatedly activated each time the animal goes through that cycle... |
Speaker A: During mating. |
Speaker C: During the mating cycle, there are also some neurons there that are active during aggression, which are distinct. And we don't know whether those neurons are there to promote aggression or to inhibit mating when animals are fighting. We have some evidence that suggests it may be the latter, but we don't know... |
Speaker A: Fascinating gal. I asked in the hopes that maybe in the years to come, your lab will parse some of the temperature relationships. And I realize it could be also regulated by hormones in general. So it's tapping into two systems for completely different reasons. Anyway, an area that intrigues me because of th... |
Speaker B: Very primitive. |
Speaker A: And yet, I think, speaks to this idea that mounting behavior might be one of the most fundamental ways in which animals, and perhaps even humans, express dominance and or sexual interactions. |
Speaker C: Yep, that's a fascinating question. And it was harder to figure out than you might have thought. So, there's been this debate for a long time in the field. When you see two male mice mounting each other, is this homosexual behavior? Is this a case of mistaken sexual identification? Or is this dominance behav... |
Speaker A: And I would say even more so when that animal is a human or is multiple humans. |
Speaker C: That's right. And there are many examples. Animals show chasing to obtain food, a prey animal that they're going to kill and eat, and they show chasing to obtain a mate that they're gonna have sex with. And so the intent of the chasing is completely different. And we don't know in all these cases whether the... |
Speaker A: I'm obsessed with dogs and dog breeds and et cetera, et cetera. And one thing I can tell you is that female dogs will mount and thrust. We had a female pit bull mixed a very sweet dog, but in observing her, it convinced me that one can never assume that male dogs are more aggressive than female dogs. It turn... |
Speaker C: Good. Yes, there is female. There are clear examples of females displaying male type mounting behavior towards other females. We see this most commonly in the lab, where we are housing females with their sisters, say three or four in a cage. We take one out, and we have her mate with a male where the male is... |
Speaker A: That has a name online. It's called a switch. |
Speaker C: Is that right? |
Speaker A: Don't ask me how I know that. Okay? But it's a pretty. Yeah, it's a term that you hear. You also hear the term topping from the bottom, which it sounds like that is a literal topping from the bottom. That's more of a psychological phrase from what I hear. I have friends that are educating me in this language... |
Speaker C: Yep. So what the function is of female mounting, I don't know. It could be a type of dominance display. It's hard to measure that because people haven't worked on female dominance hierarchies to the same extent that they've worked on male dominance hierarchies. But it indicates that the circuits for male typ... |
Speaker A: Fascinating. Fascinating. I love that paper because, as you pointed out, for chase for mounting behavior, we see it and we think one thing specifically, and after hearing this result, actually, I'm not a big fan of fight sports. I watch them occasionally cause friends are into them. But I've seen boxing matc... |
Speaker C: Good. Good. So I think of pag like an old fashioned telephone switchboard, where there are calls coming in, and then the cables have to be punched into the right hole to get the information to be routed to the right recipient on the other end of it, because pretty much every type of innate behavior you can t... |
Speaker A: That's what that peptide is. |
Speaker C: It's called bovine adrenal medullary peptide of 22 amino acid residues. And I only know about it because it activates a receptor that we discovered many years ago that's involved in pain. And we thought it promoted pain. But it turns out that this actually inhibits pain. It's like an endogenous analgesic. Wh... |
Speaker A: Sure, we appreciate those delineations. Thank you. Pag, I think this description of is an old fashioned telephone switchboard. And now every time I look into the toilet, I'll think about the periaqueductal gray. And every time I see an image of periaquel Grey, I think about. That is an excellent description ... |
Speaker C: That's right. So tachykinin refers to a family of related neuropeptides. So these are brain chemicals. They're different from dopamine and serotonin in that they're not small organic molecules. They're actually short pieces of protein that are directly encoded by genes that are active in specific neurons and... |
Speaker A: Yeah. A true shame that these companies won't do this, and especially given the fact that many of these drugs exist and their safety profiles are established, because that's always a serious consideration when embarking on a clinical trial. Perhaps in hearing this discussion, someone out there will understan... |
Speaker C: I mean, I would just. I would like to say, also, I'd like to see this tested on pets. I mean, there's a huge number of pets right now that are suffering separation anxiety because humans bought them to keep them company during the COVID pandemic. |
Speaker B: And now they're home alone. |
Speaker C: And now they're home alone. Okay. And if this thing works in mice, there's certainly a higher chance it's going to work in dogs or in cats than it is going to work in humans. And if it did, that would be even more encouragement to continue along those lines. People sometimes forget that although we work on a... |
Speaker A: Absolutely. We will put out the call. We are putting out the call. And I know for sure there will be a response just underscoring what we've been talking about even more every time we hear about a school shooting, like in Texas recently, or I happen to be in New York during the time when there was a subway s... |
Speaker C: Yes, tachycinin one is the gene name, and tachykinin two in humans is called neurokinin b. That's the name of the protein. I just refer to it by the gene name because it makes it easier and I don't have to keep remembering two names for each thing. |
Speaker A: And if I'm not mistaken, you see, you put yourself in the company of geneticists because your original training was in genetics immunology and areas related to cell biology. |
Speaker C: And I didn't actually have formal training in genetics as a graduate student, but I think I'm a geneticist at heart. That's just the way I like to think about things. And when I started working on flies, that sort of, I came out of the closet as a geneticist, as it were. |
Speaker A: Wonderful. As long as we're talking about humans, I'd love to get your thoughts about human studies of emotion. I know you wrote this book with Ralph Adolf. You have this new book which we'll provide a link to, which I've read front to back twice. It's phenomenal. I mentioned it before on the podcast. It's r... |
Speaker B: And I'm not coming to this as. |
Speaker A: A northern California mind body. I've been to Esalen once. I didn't go in the baths. I went there, I gave a talk, and I left. It is very beautiful, if anyone wants to know what it looks like. I think that final scene of Mad Men is shot at Esalen. It's a very beautiful place. And yet mind body, to me, is a ne... |
Speaker C: Good. So for the answer to the first question about the heat maps and people associating certain parts of their body with certain emotional feelings, this goes back to something called the somatic marker hypothesis that was proposed by Antonio Damasio, who is a neurologist at USC. The idea that our subjectiv... |
Speaker A: Somebody having a lot of gall. I don't know why I make a fist when I say that, but I'm guessing the gallbladder is shaped like a fist. |
Speaker C: That's right. If there is a physiology underlying these heat maps, it could reflect increased blood flow to these different structures. And that in turn reflects what you were talking about. That is, emotion definitely involves communication between the brain and the body and its bidirectional communication.... |
Speaker A: Incredible. David, I have to say, as a true fan of the work that your lab has been doing over so many decades, and first of all, I was delighted when you stopped working on stem cells, not because you weren't doing incredible work there, but because I saw a talk where you showed a, a movie of an octopus spit... |
Speaker C: I would be happy to do that. And I really have appreciated your questions. They've all been right on the money. You've hit all of the critical, important issues in this field and you've uncovered what is known, the little bit is known and how much is not known. And I think it's important to emphasize the unk... |
Speaker A: Absolutely. I second that. Well, thank you. It's been a delight. |
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