The Biology of Taste Perception & Sugar Craving | Dr. Charles Zuker

My guest this episode is Charles Zuker, Ph. D., Professor of Biochemistry, Molecular Biophysics and Neuroscience at Columbia University and an Investigator with the Howard Hughes Medical Institute. Dr. Zuker is the world’s leading expert in the biology of taste, thirst and craving. His laboratory explores the mechanisms of taste perception, focusing on how our conscious and unconscious processing of specific foods and nutrients guide our actions and behaviors. We discuss the neural circuits of taste, the “gut-brain axis,” the basis of food cravings and the key difference between wanting (craving) and liking (perceiving) sugar. We also explore how taste perception relates to specific food satiety, thirst, to our emotions, and expectation. We also consider how sugar containing and highly-processed foods can hijack the natural balance of the taste and digestive systems. Dr. Zuker provides a true masterclass in the biology of taste and perception that ought to be of interest to anyone curious about how the brain works, our motivated behaviors and the neural, chemical perceptual aspects of the mind. For the full show notes, visit hubermanlab.com. Thank you to our sponsors AG1: https://athleticgreens.com/huberman LMNT: https://drinklmnt.com/hubermanlab Waking Up: https://wakingup.com/huberman Momentous: https://livemomentous.com/huberman Timestamps (00:00:00) Dr. Charles Zuker & Taste Perception (00:03:22) Sponsors: AG1, LMNT (00:08:35) Sensory Detection vs. Sensory Perception (00:11:48) Individual Variations within Perception, Color (00:16:20) Perceptions & Behaviors (00:20:19) The 5 Taste Modalities (00:26:18) Aversive Taste, Bitter Taste (00:28:00) Survival-Based & Evolutionary Reasons for Taste Modalities, Taste vs. Flavor (00:30:14) Additional Taste Modalities: Fat & Metallic Perception (00:34:02) Tongue “Taste Map,” Taste Buds & Taste Receptors (00:39:34) Burning Your Tongue & Perception (00:42:54) The “Meaning” of Taste Stimuli, Sweet vs. Bitter, Valence (00:51:55) Positive vs. Negative Neuronal Activation & Behavior (00:56:16) Acquired Tastes, Conditioned Taste Aversion (01:01:44) Olfaction (Smell) vs. Taste, Changing Tastes over One’s Lifetime (01:09:14) Integration of Odor & Taste, Influence on Behavior & Emotion (01:17:26) Sensitization to Taste, Internal State Modulation, Salt (01:24:05) Taste & Saliva: The Absence of Taste (01:28:10) Sugar & Reward Pleasure Centers; Gut-Brain Axis, Anticipatory Response (01:36:23) Vagus Nerve (01:43:09) Insatiable Sugar Appetite, Liking vs. Wanting, Gut-Brain Axis (01:52:03) Tool: Sugar vs. Artificial Sweeteners, Curbing Appetite (01:54:06) Cravings & Gut-Brain Axis (01:57:30) Nutrition, Gut-Brain Axis & Changes in Behavior (02:01:53) Fast vs. Slow Signaling & Reinforcement, Highly Processed Foods (02:10:38) Favorite Foods: Enjoyment, Sensation & Context (02:15:58) Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Momentous Supplements, Instagram, Twitter, Neural Network Newsletter Disclaimer Learn more about your ad choices. Visit megaphone.fm/adchoices

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Andrew D. Huberman?

  Welcome to the Huberman Lab Podcast where we discuss science and science-based tools for everyday life.

• 0:09Andrew D. Huberman?

  I'm Andrew Huberman and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today, my guest is Dr. Charles Zuker. Dr. Zuker is a professor of biochemistry and molecular biophysics and of neuroscience at Columbia University School of Medicine. Dr. Zuker is one of the world's leading experts in perception. That is, how the nervous system converts physical stimuli in the world into events within the nervous system that we come to understand as our sense of smell, our sense of taste, our sense of vision, our sense of touch, and our sense of hearing. Dr. Zuker's lab is responsible for a tremendous amount of pioneering and groundbreaking work in the area of perception. For a long time, his laboratory worked on vision, defining the very receptors that allow

• 0:54Andrew D. Huberman?

  for the conversion of light into signals that the rest of the eye and the brain can understand. In recent years, his laboratory has focused mainly on the perception of taste. And indeed, his laboratory is responsible for discovering many of the taste receptors leading to our perception of things like sweetness, sourness, bitterness, saltiness, and umami, that is savoriness in food. Dr. Zuker's laboratory is also responsible for doing groundbreaking work on the sense of thirst. That is, how the nervous system determines whether or not we should ingest more fluid or reject fluids that are offered to us. A key feature of the work from Dr. Zuker's laboratory is that it bridges the brain and body. As you'll soon learn from today's discussion, his laboratory has discovered a unique set

• 1:38Andrew D. Huberman?

  of sugar sensing neurons that exist not just within the brain, but a separate set of neurons that sense sweetness and sugar within the body. And that much of the communication between the brain and body, leading to our seeking of sugar, is below our conscious detection. Dr. Zuker has received a large number of prestigious awards and appointments as a consequence of his discoveries in neuroscience. He is a member of the National Academy of Sciences, the National Academy of Medicine, and the American Association for the Advancement of Science. He is also an investigator with the Howard Hughes Medical Institute. For those of you that are not familiar with the so-called HHMI, the Howard Hughes Medical Institute. Howard Hughes Medical Institute investigators are selected on an extremely competitive basis, and indeed, they have to come back every five years and prove themselves worthy

• 2:23Andrew D. Huberman?

  of being reappointed as Howard Hughes investigators. Dr. Zuker has been a Howard Hughes investigator since 1989. What all that means for you as a viewer and/or listener of today's podcast is that you are about to learn about the nervous system and its ability to create perceptions, in particular, the perception of taste and sugar sensing, from the world's expert on perception and taste. I'm certain that by the end of today's podcast, you're not just going to come away with a deeper understanding of our perceptions and our perception of taste in particular, but indeed, you will come away with an understanding of how we create internal representations of the entire world around us, and in doing so, how we come to understand our life experience.

• 3:06Andrew D. Huberman?

  Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero-cost to consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. And now, for my discussion with Dr. Charles Zuker. Charles, thank you so much for joining me today.

• 3:27Speaker 01

  My pleasure.

• 3:29Andrew D. Huberman?

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• 5:03Andrew D. Huberman?

  And gustatory perception, but maybe to start off, and because you've worked on a number of different topics in neuroscience, not just taste.

• 5:12Andrew D. Huberman?

  How do you think about perception? Or rather, I should say, how should the world and people think about perception? How it's different from sensation? And what leads to our experience of life in terms of vision, hearing, taste, et cetera?

• 5:29Speaker 01

  So, you know, the brain is

• 5:32Speaker 01

  an extraordinary organ

• 5:36Speaker 01

  that weighs maybe 2% of your body mass, yet it consumes anywhere between 25 to 30% of all of your energy and oxygen.

• 5:51Speaker 01

  And it gets transformed into a mind.

• 5:56Speaker 01

  And this mind changes the human condition. It makes, it changes, it transforms fear into courage.

• 6:08Speaker 01

  Conformity into creativity. Sadness into happiness. How, how, how the hell does that happen?

• 6:18Speaker 01

  Now, the challenge that the brain faces is that the world is made of real things. You know, this here is a glass. And this is a cord, and this is a microphone. But the brain is only made of neurons that only understand electrical signals. So how do you transform that reality into nothing that electrical signals that now need to represent the world?

• 6:51Speaker 01

  And that process is what we can operationally define as perception. In the senses, let's say olfactory, odor, taste, vision, we can very straightforwardly separate detection from perception. Detection is what happens when you take a sugar molecule, you put it in your tongue, and then a set of specific cells now sense that sugar molecule. That's detection. You haven't perceived anything yet. That is, yes, your cells in your tongue interacting with this chemical. But now that cell gets activated and sends a signal to the brain.

• 7:35Speaker 01

  And now detection gets transformed into perception.

• 7:41Speaker 01

  And it's trying to understand how that happens. That's been the maniacal drive of my entire career in neuroscience. How does the brain ultimately transform detection into perception so that it can guide actions and behaviors? Does that make sense?

• 8:05Andrew D. Huberman?

  Absolutely, and is a very clear and beautiful description. A sort of high-level question related to that, and then I think we can get into some of the intermediate steps.

• 8:16Speaker 01

  Yes.

• 8:17Andrew D. Huberman?

  I think many people would like to know whether or not my perception of the color of your shirt is the same as your perception of the color of your shirt.

• 8:25Speaker 01

  What an excellent question. Am I okay to interrupt you as you're, as I'm guessing what you're going? All right, very good.

• 8:30Andrew D. Huberman?

  Interruption is welcome on this podcast. The audience will always penalize me for interrupting you and will never penalize you for interrupting me.

• 8:39Speaker 01

  I like the one-way penalizing. Now, given what I told you before, that the brain is trying to represent the world based in nothing but the transformation of these signals into electrical, you know, languages that now neurons have to encode and decode, it follows that your brain is different than my brain, and therefore it follows that the way that you're perceiving the world must be different than mine, even when receiving the same sensory cues, okay? And I'll tell you about an experiment, it's a simple experiment, yet brilliant, that

• 9:22Speaker 01

  demonstrates why we perceive the world, how we perceive the world different. So, in the world of vision, as you know, well, well-known, we have three classes of photoreceptor neurons that sense three basic colors, red, blue, and green. It, oh, blue, green, and red, if we go, you know, from short to long wavelength. And these three are sufficient to accommodate the full visible spectra.

• 9:57Speaker 01

  I'm gonna take three light projectors, and I'm gonna project one into a white screen,

• 10:04Speaker 01

  a red light, and the other one, green light, and wanna overlap the two beams, and on the screen, just be yellow. Okay, this is the superposition when you have two beams of red and green. And then I'm gonna take a third projector, and I'm gonna put a filter that projects right next to that mixed beam, a spectrally pure yellow.

• 10:30Speaker 01

  And I'm gonna ask you to come to the red and green projectors and play with the intensity knobs, so that you can match that yellow that you're projecting to the spectrally pure next to it. Is this making sense?

• 10:47Andrew D. Huberman?

  Perfect sense.

• 10:48Speaker 01

  And I'm going to write down the numbers in those two volume intensity knobs. And then I'm gonna ask the next person to do the same. And then I'm gonna ask every person around this area of Battery Park in New York to do the same. And guess what? We're gonna end up with thousands of different number combinations.

• 11:12Andrew D. Huberman?

  Amazing.

• 11:13Speaker 01

  Yeah? So for all of us, is yellow enough that we can use a common language? But for every one of us, that yellow is gonna be ever so slightly differently. And so I think that simple psychological experiment beautifully illustrates how we truly perceive the world differently.

• 11:36Andrew D. Huberman?

  I love that example. And yet, in that example, we know the basic elements from which color is created. If we migrate into a slightly different sense, let me pick a hard one. Like...

• 11:49Speaker 01

  Sound.

• 11:50Andrew D. Huberman?

  Sound or olfaction.

• 11:52Speaker 01

  Yeah, very hard then to do an experiment that will allow us to get that degree of granularity and beautiful causality, where we can show that A produces and leads to B. If I give you the smell of a rose, you can describe it to me. If I smell the same rose, I can describe it also. But I have no way whether the two of us are experiencing the same. But it's close enough that we can both... Pretty much say that it has the following, you know, features or other determinants.

• 12:34Speaker 01

  But no question that your experience is different than mine.

• 12:40Andrew D. Huberman?

  The fact that it's good enough for us to both survive, that your perception of yellow and my perception of yellow, at least up until now, is good enough for us both to survive.

• 12:50Speaker 01

  You got it.

• 12:51Andrew D. Huberman?

  Raises a thought about a statement made by a colleague of ours, Marcus Meister at Caltech. He's never been on this podcast, but in a review that I read by Marcus at one point, he said that the basic function of perception is to divide our behavioral responses into the outcomes downstream of three basic emotional responses. Yum, I like it. Yuck, I hate it. Or meh, whatever. What do you think about? I'm not looking to establish a debate between you, Marcus, without Marcus here.

• 13:30Speaker 01

  I understand.

• 13:31Andrew D. Huberman?

  But what I like about that is that it seems like the, we know the brain is a very economical organ in some sense, despite its high metabolic demands. And this variation in perception from one individual to the next at once seems like a problem because we're all literally seeing different things. And yet we function. We function well enough for most of us to avoid death and cliffs and eating poisons and so forth, and to enjoy some aspects of life, one hopes.

• 14:04Speaker 01

  Yes.

• 14:05Andrew D. Huberman?

  So is there a general statement that we can make about the brain? Not just as an organ to generate perception, not just as an organ to keep us alive, but also an organ that is trying to batch our behaviors into general categories of outcomes?

• 14:21Speaker 01

  I think so, but again, I think the world of Marcus too. And I think he's right that, you know, broadly speaking, you could categorize a lot of behaviors falling into those true categories. And that's 100% likely to be the case for animals in the wild.

• 14:44Speaker 01

  The choices are not necessarily binary, but they're very unique and distinct. Do I want to eat this? Do I want to kill that? Do I want to go there or do I want to go here? We humans deviated from that world long ago and learned to experience life where we do things that we should not be doing.

• 15:20Andrew D. Huberman?

  Some of us more than others.

• 15:22Speaker 01

  Exactly. You know, in my own world of taste, the likelihood that an animal in the wild will enjoy eating something bitter, it's inconceivable. Yet we, you know, love tonic water. We like living on the edge. We love enjoying experiences that makes us human. And that goes beyond that simple

• 16:03Speaker 01

  set of categories, which is yummy, yucky. Ah, who cares? And so I think it's not a bad palate, but I think it's overly reductionist for certainly what we humans do.

• 16:24Andrew D. Huberman?

  I agree. And since we're here in New York, I can say that the many options, the extensive variety of food, flora and fauna in New York explains a lot of the more nuanced behaviors that we observe. Let's talk about taste. Because while you've done extensive work in the field of vision, and it's a topic that I love, you could spend all day on, taste is fascinating. First of all, I'd like to know why you migrated from studying vision to studying taste. And perhaps in that description, you could highlight to us why we should think about and how we should think about this sense of taste.

• 17:05Speaker 01

  My goal has always been to understand, as I highlighted before, how the brain does its magic. You know, what part, you might wonder? Ideally, I like to help contribute to understand all of it. You know, how do you encode and decode emotions? How do you encode and decode memories and actions? How do you make decisions? How do you transform detection into perception? And the list goes on and on.

• 17:39Speaker 01

  But one of the key things in science, as you know, is ensuring that you always ask the right question so that you have a possibility of answering it.

• 17:52Speaker 01

  Because if the question cannot be tractable or reduced to an experimental path that helps you resolve it, then we end up doing some really fun science, but not necessarily answering the important problem that we want to study.

• 18:09Speaker 01

  Make sense?

• 18:11Andrew D. Huberman?

  From a first-person perspective, yes. The hardest question, the most important question is, what are you going, what question are you going to try and answer?

• 18:19Speaker 01

  You got it, yeah. And so, and so, for example, I would love to understand the neural basis of empathy.

• 18:28Andrew D. Huberman?

  There's a big market for that.

• 18:30Speaker 01

  100%, but, but I wouldn't even know, I mean, at the molecular level, that's what we do. How do the circuits in your brain create that sense? I have no clue how to do it. I can come up with ways to think about it, but I like to understand what in your brain makes someone a great philanthropist? What is the neural basis of love? I wouldn't even know where to begin. So if I want to begin to study these questions about brain function that can cover so many aspects of the brain, I need to choose a problem that affords me that window.

• 19:13Speaker 01

  But in a way that I can ask questions that give me answers. And among the senses that, you know, have the capacity of transforming detection into perception of being stored as memories, of creating emotions, of giving you different actions and perceptions as a function of the internal state. You know, when you're hungry, things taste very differently than when you're sated. How? Why? When you taste something, you now remember this amazing meal you had with your first date. How does that happen? All right. So if I want to begin to explore all of these things that the brain does,

• 19:58Speaker 01

  I have to choose a sensory system that affords some degree of simplicity in the way that the input-output relationships are put together. And in a way that still can be used to ask every one of these problems that the brain has to ultimately compute, encode, and decode. And what's remarkable about the taste system at the time that I began working on this is that nothing was known about the molecular basis of taste.

• 20:38Speaker 01

  You know, we knew that we could taste what has been usually defined as the five basic taste qualities: sweet, sour, bitter, salty, and umami. Umami is a Japanese word that means yummy, delicious. And that's nearly every animal species, the taste of amino acids. And in humans, it's mostly associated with the taste of MSG, monosodium glutamate, one amino acid in particular.

• 21:10Andrew D. Huberman?

  What are, just by way of example, some foods that are rich in the umami-evoking stimulation?

• 21:17Speaker 01

  Seaweed, tomatoes, cheese. And it's a great, great flavor enhancer.

• 21:26Speaker 01

  It enriches our sensory experience. And so the beautiful thing of the system is that the lines of input are limited to five.

• 21:37Speaker 01

  You know, sweet, sour, bitter, salty and umami. And each of them has a predetermined meaning. You are born liking sugar and dislike bitter. You have no choice. These are hardwired systems. But of course, you can learn to dislike sugar and to like bitter. But in the wild, let's take humans out of the equation. These are 100% predetermined. You're born with that specific valence, value for each taste.

• 22:16Speaker 01

  Sweet, umami and low salt are attractive taste qualities. They evoke appetitive responses. I want to consume them. And bitter and sour are innately predetermined to be aversive.

• 22:37Andrew D. Huberman?

  Could I interrupt you just briefly and ask a question about that exact point? For something to be appetitive and some other taste to be aversive and for those to be hardwired, can we assume that the sensation of very bitter or of activation of bitter receptors in the mouth activates a neural circuit that causes closing of the mouth, retraction of the tongue and retraction of the body and that the taste of something sweet might actually induce more licking?

• 23:10Speaker 01

  100%, you got it. The activation of the receptors in the tongue that recognize sweet versus the ones that recognize bitter activate an entire behavioral program.

• 23:24Speaker 01

  And that program that we can refer as appetitiveness or aversion, it's composed of many different subroutines. In the case of bitter, it's very easy to actually look at, see them happening in animals, because the first thing you do is you stop licking, then you put an unhappy face, then you squint your eyes, and then you start gagging. And that entire thing happens by the activation of a bitter molecule in a bitter-sensing cell in your tongue. It's incredible. It's, again, the magic of the brain, you know,

• 24:05Speaker 01

  how it's able to encode and decode these extraordinary actions and behaviors in response of nothing but a simple, very, you know, a unique sensory stimuli. Now, let me say that this palate of five basic tastes accommodates all the dietary needs of the organism. Sweet to ensure that we get the right amount of energy. Umami to ensure that we get proteins, another essential nutrient. Salt, the three appetitive ones, to ensure that we maintain our electrolyte balance. Bitter to prevent the ingestion of toxic, noxious chemicals.

• 24:47Speaker 01

  Nearly all bitter tasting, you know, things out in the wild are bad for you. And sour, most likely to prevent ingestion of spoiled acid, yeah? Fermented foods. And that's it. That is the palate that we deal with. Now, of course, there's a difference between basic taste and flavor. Flavor is the whole experience. Flavor is the combination of multiple tastes coming together.

• 25:20Speaker 01

  Together with smell, with texture, with temperature, with the look of it, that gives you what you and I would call the full sensory experience. But we scientists need to reduce the problem into its basic elements so we can begin to break it apart before we put it back together. So when we think about the sense of taste and we try to figure out how these lines of information go from your tongue to your brain and how they signal and how they get integrated and how they trigger all these different behaviors, we look at them as individual qualities. So we give the animal sweet or we give them a bitter, we give them sour. We avoid mixes.

• 26:06Speaker 01

  Because the first stage of discovery is to have that clarity as to what you're trying to extract so that you can hopefully meaningfully make a difference by being able to figure out how is it that A goes to B to C and to D. Does this make sense?

• 26:26Andrew D. Huberman?

  Yeah, almost like the primary colors to create the full array of the color spectrum.

• 26:30Speaker 01

  Exactly.

• 26:32Andrew D. Huberman?

  Before I ask you about the first and second and third stages of taste and flavor perception, is there any idea that there may be more than five?

• 26:42Speaker 01

  There is, for example. What about fat?

• 26:46Andrew D. Huberman?

  I love the

• 26:47Speaker 01

  I love fat too.

• 26:48Andrew D. Huberman?

  And I love the texture of fat, especially if it's slightly burnt, like the in South America, when I visited Buenos Aires, I found that at the end of a meal, they would take a steak, the trimming off the edge of the steak, burn it slightly and then serve it back to me and I thought, that's disgusting. And then I tasted it and it's delightful.

• 27:08Speaker 01

  It is.

• 27:09Andrew D. Huberman?

  There's nothing quite like it.

• 27:11Speaker 01

  This goes back to this notion before that we like to live on the edge. And we like to do things that we should not be doing, Andrew. But on the other hand, look at those muscles.

• 27:23Andrew D. Huberman?

  The, uh, the, uh, I don't suggest anyone eat pure fat. The listeners of this podcast will immediately, I'm sure there'll be a YouTube video soon that I like eating pure fat. I'm not in, on a ketogenic diet, et cetera, but, um, but fat is tasty. As evidenced by the obesity problem that exists in this country.

• 27:43Speaker 01

  We'll talk about that, you know, in a little bit about the, you know, the gut-brain axis. I think it would be important to cover it because it's the other side of the taste system. And, and so, so missing taste, you know, one is fat. Although like you clearly highlighted, a lot of fat taste, in quotation marks, is really the feeling of fat rolling on your tongue. And so there is a, a, a compelling argument that a lot of what we call fat taste is really mechanosensory.

• 28:25Speaker 01

  It's somatosensory cells, cells that are not responding to taste, but they're responding to mechanical stimulation of fat molecules rolling on the tongue that gives you that perception of fat.

• 28:40Andrew D. Huberman?

  I love the idea that there is a perception of fat, regardless of whether or not there's a dedicated receptor for fat. Mostly because it's making evoking sensations and imagery of, of the taste of slightly burnt fat.

• 28:54Speaker 01

  For, for example, and another one, you know, you could argue is metallic taste. You know, I know exactly what it tastes like. You know, if you ask me to explain it, I will have a hard time. You know, what, whether the palettes of that color that can allow me to define it, I, I, I wouldn't be easy, but I know precisely what it tastes like, you know, take a, take a penny, put it in your mouth and you know what it tastes like, yeah?

• 29:21Andrew D. Huberman?

  Or blood.

• 29:21Speaker 01

  Or blood, that's another very good example.

• 29:25Speaker 01

  And is there really, you know, a receptor for metallic taste? Or it's nothing but this magical combination of the activation of the existing lines? Think of it as lines of information, yeah, separate lines, like the keys of a piano, yeah? Sweet, sour, bitter, salty, umami, you play that key and you activate that one chord. And that one chord, in the case of a piano, leads to a note, you know, a tune. And in the case of taste, leads to an action and a behavior. But you play many of them together and something emerges that it's different than any one of the pieces. And it's possible that metallic, for example,

• 30:07Speaker 01

  represents the combination of the activity just in the right ratio of these other lines.

• 30:16Andrew D. Huberman?

  Makes sense. And it actually provides a perfect, your example of the piano provides a perfect segue for what I'd like to touch on next, which is, if you would, describe the sequence of neural events leading to a perceptual event of taste. And I'm certain that somewhere in there, you will embed an answer to the question of whether or not we indeed have different taste receptors distributed in different locations on our tongue or elsewhere in the mouth.

• 30:47Speaker 01

  Yes. So let's start by debunking that old tale and myth.

• 30:55Andrew D. Huberman?

  Who came up with that?

• 30:57Speaker 01

  There are many views, but the most prevalent is that there was an original drawing describing the sensitivity of the tongue to different tastes. So imagine I can take a Q-tip. This is a thought experiment, yeah? And then when I dip that Q-tip in salt and in quinine, something bitter, and glucose or something sweet. And I'm gonna take that Q-tip, ask you to stick your tongue out and start moving it around your tongue and ask you, what do you feel?

• 31:37Speaker 01

  And then I'm going to change the concentration of the amount of salt or the amount of bitter and ask, can I get some sort of a map of sensitivity to the different tastes?

• 31:51Speaker 01

  And the argument that has emerged is that there is a good likelihood that the data was simply mistranslated as it was being drawn.

• 32:03Speaker 01

  And of course, that led to an entire industry. This is the way you maximize your wine experience. Because now we're going to form the vessel that you're going to drink from so that it acts maximally on the receptors which happen, alright. Now, there is no tongue map. Alright? We have taste buds distributed in various parts of the tongue, so there is a map on the distribution of taste buds. But each taste bud has around 100 taste receptor cells. And those taste receptor cells can be of five

• 32:46Speaker 01

  types, sweet, sour, bitter, salty, or umami. And for the most part,

• 32:54Speaker 01

  all taste buds have the representation of all five taste qualities. Now, there is no question that there is a slight bias for some tastes. Like bitter is particularly enriched at the very back of your tongue. And there is a teleological basis for that, actually a biological basis for that. That's the last line of defense before you swallow something bad.

• 33:21Speaker 01

  And so let's make sure that the very back of your tongue has plenty of these bad news receptors so that if they get activated, you can trigger a gagging reflex. And get rid of this that otherwise may kill you.

• 33:38Andrew D. Huberman?

  That's good sense.

• 33:39Speaker 01

  But the notion that, you know, all Swedish in the front and Saudis on the side,

• 33:47Speaker 01

  it's not real. And they're, go ahead.

• 33:51Andrew D. Huberman?

  Oh, I was just gonna ask, are there, first of all, thank you for dispelling that myth.

• 33:55Speaker 01

  Yes.

• 33:55Andrew D. Huberman?

  And we will propagate that information as far and wide as we can, because I think that's the number one myth related to taste. The other one is, are there taste receptors anywhere else in the mouth? For instance, on the lips?

• 34:09Speaker 01

  The palate, not the lips. So it's in the pharynge, at the very back of the oral cavity, the tongue and the palate. And the palate is very rich in sweet receptors.

• 34:21Andrew D. Huberman?

  I'll have to pay attention to this the next time I eat something sweet.

• 34:24Speaker 01

  Whether you pull it up, yeah? Now, the important thing is that, you know, after the receptors for these five, the detectors, the molecules that sense sweet, sour, bitter, salt to mommy, these are receptors, proteins found on the surface of taste receptor cells that interact with these chemicals. And once they interact, then they trigger the cascade of events, biochemical events inside the cell that now sends an electrical signal that says there is sweet here or there is salt here. Now, having these receptors, and my laboratory identify the receptors for all five basic taste classes,

• 35:09Speaker 01

  sweet, bitter, salt, umami, and most recently sour, now completing the palate, you can now use these receptors to really map where are they found in the tongue in a very rigorous way. This is no longer about using a Q-tip and trying to figure out what you're feeling, but rather what you have in your tongue.

• 35:33Speaker 01

  This is not a guess. This is now a physical map that says the sweet receptors are found here. The bitter are found here. And when you do that, you find that in fact, every taste bud throughout your oral cavity has receptors for all of the basic taste classes.

• 35:54Andrew D. Huberman?

  Amazing. And as it turns out, and I'm sure you'll tell us, important in terms of thinking about how the brain computes and codes and decodes this thing we call taste.

• 36:05Speaker 01

  Yes.

• 36:05Andrew D. Huberman?

  I'm going to inject a quick question that I'm sure is on many people's minds before we get back into the biological circuit, which is many people, including myself, are familiar with the experience of drinking a sip of tea or coffee that is too hot. And burning my tongue is the way I would describe it. Horrible. And then disrupting my sense of taste for some period of time afterward.

• 36:27Speaker 01

  Yes.

• 36:28Andrew D. Huberman?

  When I experienced that phenomenon, that unfortunate phenomenon, have I destroyed taste receptors that regenerate? Or have I somehow used temperature to distort the function of the circuit so that I no longer taste the way I did before?

• 36:45Speaker 01

  Excellent question, and the answer is both. It turns out that your taste receptors only live for around two weeks. And this, by the way, makes sense because here you have an organ, the tongue, that is continuously exposed to everything you could range from the nicest to the most horrible possible things.

• 37:09Andrew D. Huberman?

  Use your imagination.

• 37:11Speaker 01

  And so you need to make sure that these cells are always coming back in a way that I can re-experience the world in the right way. And there are other organs that have the same underlying logic, okay? Your gut, your intestines are the same way. Amazing. Again, they are receiving everything that you ingest, God forbid what's there, from the spiciest, you know, to the most horrible tasting, to the most delicious. And again, those intestinal cells whose role is to ultimately take all these nutrients and bring them into the body, also renew.

• 37:57Speaker 01

  In a very, very fast cycle.

• 38:03Speaker 01

  Olfactory neurons in your nose is the other example.

• 38:07Speaker 01

  So then, A, yes, you're burning a lot of your cells and it's over for those. The good news is that they're gonna come back. But we know that when you burn yourself with T-DIG, come back, you know, within 20 minutes, 30 minutes, an hour. And these cells are not renewing in that timeframe. They're not listening to your needs. They have their own internal clock.

• 38:35Speaker 01

  And so you are really affecting, you're damaging them in a way that they can recover. And then they come back and you also damage your somatosensory cells. These are the cells that feel things, not taste things.

• 38:56Speaker 01

  And then, you know, you wait half an hour or so and then, my goodness, thank God, it's back to normal.

• 39:04Andrew D. Huberman?

  Yeah, and most of the time, I don't even notice the transition, realizing, as you told me. And later, I'll ask you about the relationship between odor and taste. But as a next step along this circuit, let's assume I ingest some, let's keep it simple, a sweet taste.

• 39:22Speaker 01

  Let's make it even simpler, but at the same time, perhaps more informative. Let's compare and contrast sweet and bitter as we follow their lines from the tongue to the brain.

• 39:39Speaker 01

  So the first thing is that the two evoke diametrically opposed behaviors. If we have to come up with two sensory experiences that represent polar opposites, it will be sweet and bitter. There are no two colors that represent polar opposites because, you know, you could say black and white, they are polar opposites, one detects only one thing, the other one detects everything. But they don't evoke different behaviors.

• 40:04Andrew D. Huberman?

  Even political parties have some overlap.

• 40:08Speaker 01

  Sweet and bitter are the two opposite ends of the sensory spectrum. Now, a taste...

• 40:16Speaker 01

  Can be defined by two features. Again, I'm a reductionist. So I'm reducing it in a way that I think it's easier to follow the signal. And the two features are its quality and its valence. And valence with a little v, that's what we say in Spanish with a v, means the value of that experience. All right? Or in this case of that stimuli. And you take sweet. Sweet has a quality, an identity. And that's what you and I will refer to as the taste of sweet.

• 41:00Speaker 01

  We know exactly what it tastes like. But sweet also has a positive valence, which makes it incredibly attractive and appetitive. But it's attractive and appetitive, as I'll tell you in a second, independent of its identity and quality. In fact, we have been able to engineer animals where we completely remove the valence from the stimuli. So these animals can taste sweet, can recognize it as sweet, but it's no longer attractive. It's just one more chemical stimuli. And that's because the identity and the valence

• 41:43Speaker 01

  are encoded in two separate parts of the brain. In the case of bitter, again, it has, on the one hand, its identity, its quality. And you know exactly what bitter tastes like.

• 41:58Andrew D. Huberman?

  I can taste it now, even as you describe it.

• 42:01Speaker 01

  But it also has a valence. And that's a negative valence because it evokes aversive behaviors. Are we on?

• 42:10Andrew D. Huberman?

  Absolutely. And it comes to mind, I remember telling some kids recently that we're gonna go get ice cream. And it was interesting, they looked up and they started smacking their lip like, you know, they'll actually.

• 42:19Speaker 01

  The anticipatory response, absolutely. When we talk about the gut brain, maybe we'll get there. So then the signals, if we follow now these two lines, they're really like two separate keys at the two ends of this keyboard.

• 42:36Speaker 01

  And you press one key and you activate this cord. So you activate the sweet cells throughout your oral cavity. And they all converge into a group of sweet neurons in the next station, which is still outside the brain. It's one of the taste ganglia. These are the neurons that innervate your tongue and the oral cavity. Where do they sit approximately? Around there. Yeah, right here around the blood lymph nodes, more or less. You got it. And there are two main ganglia that innervate the vast majority of all taste buds in the oral cavity.

• 43:18Speaker 01

  And then, from there, that sweet signal goes on to the brainstem. The brainstem is the entry of the body into the brain. And there are different areas of the brainstem. And there are different groups of neurons in the brainstem. And there's a unique area, in a unique, a topographically defined location in the rostral side of the brainstem that receives all of the taste input. A very dense area of the brain. A very rich area of the brain, exactly. And from there, this sweet signal goes to this other area, higher up

• 44:03Speaker 01

  on the brainstem. And then it goes through a number of stations where that sweet signal goes from sweet neuron to sweet neuron to sweet neuron to eventually get to your cortex. And once it gets to your taste cortex, that's where meaning is imposed into that signal. It's then, and only then, this is what the data suggests, that now you can identify this as a sweet stimuli. And how quickly does that all happen?

• 44:43Speaker 01

  You know, the timescale of the nervous system, it's fast, yeah?

• 44:49Andrew D. Huberman?

  Within less than a second.

• 44:51Speaker 01

  Yeah, absolutely, yeah.

• 44:53Andrew D. Huberman?

  I rarely mistake bitter for sweet.

• 44:55Speaker 01

  Yeah.

• 44:56Andrew D. Huberman?

  Maybe with respect to people and my own poor judgment, but...

• 44:59Speaker 01

  But no.

• 45:00Andrew D. Huberman?

  But not with respect to taste.

• 45:01Speaker 01

  Yeah, it's... And in fact, we can demonstrate this because we can stick electrodes at each of these stations, conceptually, yeah? And we can stimulate the tongue and then we can record the signals, pretty much time lock to stimulus delivery. You deliver the stimuli and within a fraction of a second,

• 45:21Speaker 01

  you see now the response in these following stations. Now it gets to the cortex, yeah? And now, in there, you impose meaning to that taste. There is an area of your brain that represents the taste of sweet in taste cortex, and a different area that represents the taste of bitter. In essence, there is a topographic map of these taste qualities inside your brain.

• 45:52Speaker 01

  Now, we're going to do a thought experiment, alright? Now, if this group of neurons in your cortex really represents the sense of sweet, and this added different group of neurons in your brain represents the taste, the perception of bitter, then we should be able to do two things. First, I should be able to go into your brain, somehow silence those neurons, find a way to prevent them from being activated,

• 46:27Speaker 01

  and I can give you all the sweet you want, and you'll never know that you're tasting sweet.

• 46:33Speaker 01

  And conversely, I should be able to go into your brain, come up with a way to activate those neurons, while I'm giving you absolutely nothing, and you're gonna think that you're getting that full percept.

• 46:51Speaker 01

  And that's precisely what we have done, and that's precisely what you get. This, of course, is in the brain of mice.

• 46:58Andrew D. Huberman?

  But presumably, in humans, it would work similarly.

• 47:00Speaker 01

  Absolutely the same, zeroed out. I have no questions. So this attests to two important things. The first, to the predetermined nature of the sense of taste.

• 47:15Speaker 01

  Because it means I can go to these parts of your brain in the absence of any stimuli and have you throw the full behavioral experience. In fact, when we activate in your cortex these bitter neurons, the animal can start gagging.

• 47:33Speaker 01

  But it's drinking only water.

• 47:38Speaker 01

  But the animal thinks that it's getting a bitter stimuli.

• 47:43Andrew D. Huberman?

  This is amazing.

• 47:44Speaker 01

  And so, and the second, just to finish the line so that it doesn't sound like it teaches two things and then I only give you one lesson.

• 47:55Speaker 01

  Is that, you know, it substantiates this capacity of the brain to segregate, to separate in these nodes of action, the representation of these two diametrically opposed percepts, which is sweet, for example, versus bitter.

• 48:14Andrew D. Huberman?

  The reason I say amazing, and that is also amazing, is the following.

• 48:20Andrew D. Huberman?

  You told us earlier, and you're absolutely correct, of course, that the end of the day, whether or not it's one group of neurons over here and another group of neurons over there, which is the way it turns out to be, electrical activity is the generic, common language of both sets of neurons. So that raises the question for me of whether or not those separate sets of neurons are connected to areas of the brain that create this sense of valence, or whether or not they're simply created, connected, excuse me, to sets of neurons that evoke distinct behaviors of moving towards and inhaling more and licking or aversive. Are we essentially interpreting our behavior and our microresponses? Or are microresponses in our behaviors the consequence of the percep?

• 49:05Speaker 01

  Excellent, excellent question. So first, the answer is they go into an area of the brain. Where valence is imposed. And that area is known as the amygdala. And the sweet neurons go to a different area than the bitter neurons. Now, I want to do a thought experiment because I think your audience might appreciate this. Let's say I activate this group of neurons, and the animal increases licking. And I'm activating the sweet neurons. And so that's expected because now it's tasting this water as if it was sugar.

• 49:48Speaker 01

  Now, this is Moses transforming water into wine. In this case, we're going to... And today's Passover, so then it's an appropriate, you know, example. We're transforming it into sweet, yeah? But how do I know? How do I know that activating them is evoking a positive feeling inside? A goodness, a satisfaction, oh, I love it, versus I'm just increasing licking? Which is the other option, because all we're seeing is that the animal is licking more, and we're trying to infer that that means that it's feeling something really good versus, you know what? That piano line is going back straight into the tongue,

• 50:31Speaker 01

  and all it's doing is forcing it to move faster. Well, we can actually separate this by doing experiments that allows to fundamentally distinguish them. And imagine the following experiment. I'm going to take the animal and I'm going to put him inside a box that has two sides. And the two sides have features that make him different. One has yellow little toys, the other one has green toys. One has little, you know, black stripes, the other one has blue stripes. So the animal can tell the two halves. I take the mouse, put him inside this arena, this play arena,

• 51:13Speaker 01

  and it will explore and put around both sides with equal frequency. And now what I'm going to do is I'm going to activate these neurons, the sweet neurons, every time the animal is on the side with the yellow stripes.

• 51:34Speaker 01

  And if that is creating a positive internal state, what would the animal now want to do? It will want to stay on the side with the yellow stripes. There is no leaking here. The animal is not extending its tongue every time I'm activating these neurons. This is known as a place preference test. And it's generally used, it's just one form of many different tests to demonstrate that the activation of a group of neurons in the brain is imposing, for example, a positive versus a negative valence.

• 52:19Speaker 01

  Whereas if they do the same thing by activating the bitter neurons, the animal will actively want now to stay away from the side where these neurons are being activated. And that's precisely what you see.

• 52:33Andrew D. Huberman?

  And that's precisely what we see. Many people, including myself, are familiar with the experience of going to a restaurant, eating a variety of foods, and then, fortunately, it doesn't happen that often, but then feeling very sick. I learned, coming up in neuroscience, that this is one strong example of one trial learning, that from that point on, it's not the restaurant, or the waitress, or the waiter, or the date, but it's my notion of it had to have been the shrimp that leads me to then want to avoid shrimp in every context, maybe even shrimp powder.

• 53:11Speaker 01

  You got it.

• 53:12Andrew D. Huberman?

  For a very long time. I can imagine all the evolutionary adaptive reasons why this such a phenomenon would exist. Do we have any concept of where in this pathway?

• 53:22Speaker 01

  We do. We know actually a significant amount...

• 53:27Speaker 01

  At a general level, yeah. In fact, more than shrimp, oysters are even a more dramatic example, yeah. One bad oyster is all you need to be driven away for the next six months.

• 53:41Andrew D. Huberman?

  I think because of the texture alone is something that one learns to overcome. I actually really enjoy oysters. I despise mussels, despise shrimp, not the animal, but the taste. And yet, oysters, for some reason, I've yet to have a bad experience.

• 53:56Speaker 01

  It's like uni, by the way, you know, texture is hard to get over. But once you get over, it's delicious.

• 54:02Andrew D. Huberman?

  That's what they tell me. We were both in San Diego at one point and I'll give a plug to sushi otas, kind of the famous little sushi. And they have amazing uni and I've tried it twice and I'm 0 for 2. Somehow, the texture outweighs any kind of the deliciousness that people report.

• 54:19Speaker 01

  It's a very acquired taste, yeah. It's like beer, you know, if you... I grew up in Chile. That's where the accent comes from, in case anyone wonder. And you know, by the time I came here to graduate school, I was 19, too old to, you know, overkind my heavy Chilean accent. So here I am, 40 years, 50 years later, not quite, 40 plus.

• 54:43Andrew D. Huberman?

  We appreciate it.

• 54:44Speaker 01

  And I still sound like I just came off the boat. So in Chile, you don't drink beer when you're young. You drink wine, you know, Chile is a huge wine producer. So when I came to the US, all of my classmates, you know, were drinking beer. Because they, you know, they had finished college where they were all, you know, beer drinking and, you know, graduate school, you're working 18 hours a day, every day. The way they, you know, relax, let's go and have some beers.

• 55:15Andrew D. Huberman?

  And beer is cheaper.

• 55:16Speaker 01

  And beer is cheap. And we were being clearly underpaid, may I add.

• 55:24Speaker 01

  I couldn't do it. It's an acquired taste. It was too late by then. And here I am, you know, sixty plus. And if you take all the beer I've drunk in my entire life, I would say they add to less than an eight ounce glass of water.

• 55:40Andrew D. Huberman?

  Impressive. Well, your health is probably better for it.

• 55:43Speaker 01

  I'm not sure.

• 55:45Andrew D. Huberman?

  Your physical health, anyway.

• 55:46Speaker 01

  So, you know, it goes back to, you know, acquired taste. This is the connection to uni and to oysters. Now, going back to the one trial learning. You know, this is the great thing about our brains. Certain things, we need to repeat a hundred times to learn them. Hello, operator, can I have the phone number for sushi otta, please? And then she'll give it to you over the phone, at least in the old days. And then you need to repeat it to yourself over and over and over the next minute, so you can dial sushi otta. And five minutes later, it's gone. That's what we call working memory.

• 56:26Speaker 01

  Then there is the short-term memory. We park our car. And if we're lucky, by the end of the day, we remember where it is. And then there is the long-term memory. We remember the birthdays of every one of our children for the rest of our lives. Well, there are events, that a single event is so traumatic,

• 56:47Speaker 01

  that it activates the circuits in a way that it's a one-trial learning. And the taste system is literally at the top of that food chain. And there is a phenomenon known as conditioned taste aversion.

• 57:04Speaker 01

  You can pair an attractive stimuli with a really bad one.

• 57:12Speaker 01

  And you can make an animal begin to vehemently dislike, for example, sugar.

• 57:19Speaker 01

  And that's because you've conditioned the animals to now be averse to this otherwise nice taste because it's been associated with malaise. And when you do that, now you could begin to ask, what has changed in the signal as it travels from the tongue to the brain in a normal animal versus an animal where you have now transformed sweet from being attractive to being aversive? And this is the way now you begin to explore how the brain changes the nature, the quality, the meaning of a stimuli as a function of its state.

• 58:03Andrew D. Huberman?

  I have a number of questions related to that, all of which relate to this idea of context. Because you mentioned before that flavor is distinct from taste because flavor involves smell, texture, temperature, and some other features. Ooni, sea urchin being a good example of, I can sense the texture. It actually, no, I won't describe what it reminds me of for various reasons. The ability to place context into, to insert context into a perception, or rather to insert a perception into context is so powerful.

• 58:42Andrew D. Huberman?

  And there's an element of kind of mystery about it, but if we start to think about some of the more nuance, that we like to live at the edge, as you say, how many different tastes on the taste dial, to go back to your analogy earlier, the color dial, do you think that there could be for something as fixed as bitter? So for instance, I don't think I like bitter tastes, but I like some fermented foods that seem to have a little bit of sour and have a little bit of that briny flavor. How much plasticity do you think there is there, and in particular across the lifespan? Because I think one of the most salient examples of this is that kids don't seem to like certain

• 59:26Andrew D. Huberman?

  vegetables, but they all are hardwired to like sweet tastes. And yet, you could also imagine that one of the reasons why they may eventually grow to incorporate vegetables is because of some knowledge that vegetables might be

• 59:39Speaker 01

  Good for you.

• 59:40Andrew D. Huberman?

  Better for them. So is there a change in the receptors? The distribution, the number, the sensitivity, etc. That can explain the transition from wanting to avoid vegetables to being willing to eat vegetables. Simply in childhood to early development.

• 59:56Speaker 01

  I'm gonna take the question slightly differently, but I think it will illustrate the point. And I'm gonna just use the difference between the olfactory system and the taste system to make the point.

• 1:00:12Speaker 01

  Taste system, five basic palettes. Sweet, sour, bitter, salty, and umami. Each of them has a predetermined identity. We know exactly what to... And valence. These are attractive, these are aversive. In the olfactory system, it's claimed that we can smell millions of different odors.

• 1:00:30Speaker 01

  Yet, for the most part, none of them have an innate predetermined meaning. In the olfactory system, meaning is imposed by learning and experience.

• 1:00:45Andrew D. Huberman?

  Even the smell of smoke?

• 1:00:47Speaker 01

  So, I'm gonna give you... I'm gonna make it differently. There are a handful of the millions of odors that were claimed that you could immediately tell me these are aversive and these are attractive.

• 1:01:01Andrew D. Huberman?

  Vomit.

• 1:01:02Speaker 01

  So, vomit, it's not correct, because I can assure you that there are cultures and societies where things which are far less appealing than vomit do not evoke an aversive reaction.

• 1:01:15Andrew D. Huberman?

  Really?

• 1:01:16Speaker 01

  Really. Sulfur would be maybe a universal. I'm not talking pheromones, okay? Pheromones are in a different category that trigger innate responses. But nearly every odor is afforded meaning by learning and experience. And that's why you like broccoli, and I despise broccoli, because I remember my mother forcing me to eat broccoli. Same sensory experience!

• 1:01:44Andrew D. Huberman?

  Yeah, alright.

• 1:01:47Speaker 01

  This accommodates two important things. In the case of taste, you have neurons at every station that are for sweet, for sour, for bitter, for salty and umami. It's only five classes, so it's not going to take a lot of your brain. If we can in fact smell a million odors, and every one of those odors had to have predetermined meaning, there is not going to be enough brain just to accommodate that one sense. And so evolution in its infinite wisdom, evolve a system where you put together a pathway and a cortex, olfactory cortex,

• 1:02:26Speaker 01

  where you have the capacity to associate every odor in a specific context that now gives it the meaning. Now, let's go back to the original question then. So, other than clearly plastic, mega-plastic, because it's fundamental basis and neural organization. But taste, we just told you that's predetermined hardwire. But predetermined hardwire doesn't mean that it's not modulated by learning or experience. It only means that you are born liking sweet and disliking bitter.

• 1:03:10Speaker 01

  And we have many examples of plasticity, beer being one example. So why do we learn to love beer? It's in coffee. It's because it has an associated gain to the system. And that gain to the system, that positive valence that emerges out of that negative signal is sufficient to create that positive association. And in the case of beer, of course, is alcohol. The feeling good that we get after is more than sufficient to say, "I want to have more of this." And in the case of coffee, of course, is caffeine activating a whole group of neurotransmitter systems

• 1:03:55Speaker 01

  that give you that high associated with coffee. So yes, this taste system is changeable, it's malleable, and is subjected to learning and experience. But unlike the olfactory system, it's restricted in what you could do with it because its goal... Is to allow you to get nutrients and survive. The goal of the olfactory system is very different. It's being used, not in our case, but in every animal species, to identify friend versus foe, to identify mate, to identify ecological niches they wanna be in.

• 1:04:38Speaker 01

  So it plays a very broad role that then requires that it be set up, organized, and function in a very different type of context. Taste is about can we get the nutrients we need to survive? And can we ensure that we are attracted to the ones we need? And we are versed to the ones that are going to kill us? I'm being overly simplistic and reductionist, but I think it illustrates a huge difference between these two chemosensory systems.

• 1:05:10Andrew D. Huberman?

  I don't think you've been overly simplistic. I think it illustrates the key and tractable nature of this system and the way you've approached it. And I think it's important for people to hear that. Because everybody, as we are mystified with empathy and love, etc. So in fairness to that, I'm gonna ask a sort of a high-level question or abstract question. This was based on a conversation I had with a former girlfriend, where we were talking about chemistry between individuals.

• 1:05:41Speaker 01

  Yes.

• 1:05:41Andrew D. Huberman?

  Very complicated topic on the one hand, but on the other hand, quite simple in that certain people, for whatever reason, evoke a tremendous sense of arousal, for lack of a better word, between two people, one would hope. At least for some period of time.

• 1:06:02Speaker 01

  I didn't know this was that kind of a podcast.

• 1:06:04Andrew D. Huberman?

  No, well, the reason I... But this has to do with taste, because she said something, I think in part to maybe irritate me a bit. But we were commenting not about our own experience of each other, but of someone that she was now very excited about. We're on good terms.

• 1:06:23Speaker 01

  Uh-huh.

• 1:06:25Andrew D. Huberman?

  And she said, "What do you think it is, this thing of chemistry?" So maybe she was trying to, you know...

• 1:06:31Speaker 01

  Warn you of what's coming.

• 1:06:33Andrew D. Huberman?

  Warn me what's coming. And she said, "I have a feeling something about it is in smell." And something about it is actually in taste, literally the taste of somebody's breath. That's the way she described it. And I thought that was a very interesting example for a number of reasons. But in particular, because it gets to the merging of odor and taste. But also to the idea that, of course, the context of a new relationship. I'm assuming, and in fact, they're both attractive people, et cetera. There's a whole context there. But I've had the experience of the odor of somebody's breath being aversive, not because I could identify it as aversive.

• 1:07:16Speaker 01

  Because you just didn't like it.

• 1:07:17Andrew D. Huberman?

  But because it just didn't like it.

• 1:07:20Speaker 01

  But that's because you associate it with other odors that trigger that negative, you know, aversive reaction, by the way.

• 1:07:35Andrew D. Huberman?

  Absolutely. There are certain perfumes to me that are aversive.

• 1:07:38Speaker 01

  You got it.

• 1:07:39Andrew D. Huberman?

  And there are other scents, I can recall scents of skin, of foods, et cetera, that are immensely appetitive. So I've experienced both sides of this equation myself. And she was describing this, and to me, more than tasting wine, which is the typical example, where people inhale it and then they drink it. To me, this seems like something that more people might be able to relate to. That certain things and people smell delicious. Even mothers describing the smell of their baby's head.

• 1:08:09Speaker 01

  A mother's ass. I mean, our own babies, when they're in their necks. That's the magical place.

• 1:08:16Andrew D. Huberman?

  Their neck.

• 1:08:17Speaker 01

  The back of their neck.

• 1:08:18Andrew D. Huberman?

  There you go.

• 1:08:18Speaker 01

  Oh, my goodness. I have a grandchild now, so I know exactly what Rio, that's his name, smells like.

• 1:08:25Andrew D. Huberman?

  Okay, so more beautiful examples. It's always more fun to think about the beautiful, positive, appetitive examples. The smell of the back of your grandson's neck.

• 1:08:34Speaker 01

  Yes.

• 1:08:35Andrew D. Huberman?

  I mean, you couldn't, you could get more specific than that, but not a lot more specific. So what is going on in terms of the combination of odor and taste, given that these two systems are so different?

• 1:08:47Speaker 01

  Yes. And they come together.

• 1:08:52Speaker 01

  Ultimately, there is a place in the brain where they come together to integrate the two into what we would call, you know, that sensory experience. And I'll tell you an experiment that you could do that demonstrates this. I think in, in, in, I think it's good for the, you know, for, for, for your audience here to get a sense of how we approach these problems, so that we can get, you know, meaningful scientific answers.

• 1:09:20Speaker 01

  So we know where the olfactory cortex is in the brain. We know where the taste cortex is in the brain. They're in two different places. We can go to each of these two cortices, put color traces, we put green in one, we put red in the other, and we see where the colors go to. That's a reflection of where those neurons are projection, are projecting to, into their next targets. Once they get the signal, where do they send the signal to? And then we reason that if odor and taste come together somewhere in the brain, we should find an area that now it's getting red and green color.

• 1:10:03Speaker 01

  And we found such an area. And next, we anticipated, we hypothesized that maybe this is the area in the brain of the mouse, corresponding area in the brain of humans, that integrates odor and taste. It's known, this, the term normally used is multi-sensory integration. And if this is true, we could do the following experiment. We can train a mouse to lick sweet. And if they guess correctly that that is supposed to be sweet,

• 1:10:45Speaker 01

  they should go now to the right port, to the right side, to get a water reward.

• 1:10:54Speaker 01

  If they go to the left when it was sweet, then they are incorrect and they get no reward. And they actually get a timeout. Now, the mice are thirsty, so they're very motivated to perform. And if you repeat this task 100 times, 100 trials, incredibly enough, this animal learned to recognize the sweet and execute the right action. And by their action, we now are being told what that animal is tasting. We can make it more interesting and we can give him sweet and bitter and say if it's sweet, go to the right and if it's bitter, go to the left. And after you train him, these mice with 90% accuracy will tell you,

• 1:11:39Speaker 01

  when you randomize now the stimuli, what was sweet and what was bitter. All right. We can now do the same experiment, but now mix taste with odor. And say if you got odor alone, go to the right or push this lever. In mice, if you get taste alone, go to this other part or push this other lever. And if you get the two together, do this something else. And if you train the mice, the mice are able now to report back to you when it's sensing taste alone, odor alone, or the mix.

• 1:12:24Speaker 01

  Make sense?

• 1:12:25Andrew D. Huberman?

  Makes sense.

• 1:12:26Speaker 01

  Now, we can go to the brain of these mice and go to this area that we now uncover, discover as being the site of multisensor integration between taste and odor and silence it, prevent it from being activated experimentally. And if that area really represented the integration of these two, the animals should still be able to recognize the taste alone. They still should be able to recognize the odor alone, but should be incapable now to recognize the mix.

• 1:13:04Speaker 01

  And exactly as predicted, that's exactly what you get, alright?

• 1:13:09Andrew D. Huberman?

  The brain is basically a series of engineered circuits. Complex.

• 1:13:15Speaker 01

  You got it. And our task is, you know, to figure out how can we extract,

• 1:13:22Speaker 01

  you know, this amazing architecture of these circuits in a way that we can begin to uncover the mysteries, you know, of the brain.

• 1:13:32Andrew D. Huberman?

  And why certain people's breath tastes so good and other people's not so good.

• 1:13:38Speaker 01

  So I never answered that, but I told you how we can figure out where in the brain is happening.

• 1:13:45Andrew D. Huberman?

  As we've been having this discussion, I thought a few times about similarities to the visual system or differences to the visual system. The visual system, there are a couple of phenomenon that I wonder if they also exist in the taste system. In the visual system, we know, for instance, that if you look at something long enough and activate the given receptors long enough, that object will actually disappear. We offset this with little micro eye movements, etc. But the principle is a fundamental one, this habituation or desensitization. Everyone seems to call it something different, but you get the idea, of course. In the taste system, I'm certainly familiar with eating something very, very sweet for the first time in a long time, and it feels, tastes very sweet.

• 1:14:29Andrew D. Huberman?

  But a few more licks, a few more bites, and now it tastes not as sweet. With olfaction, I'm familiar with the odor in a room I don't like or I like, and then it disappearing. So similar phenomenon.

• 1:14:41Andrew D. Huberman?

  Where does that occur? And can you imagine a sort of a system by which people could leverage that? Because I do think that most people are interested in eating not more sugar, but less sugar.

• 1:14:57Speaker 01

  I think we have better ways to approach that. And we can transition from taste into these other circuits that makes sugar so extraordinarily impossible not to consume.

• 1:15:13Andrew D. Huberman?

  Impossible?

• 1:15:14Speaker 01

  Exactly. So where does this, this desensitizing happens? That's the term that we use it.

• 1:15:26Speaker 01

  It's, I think, happening at multiple stations. It's happening at the receptor level, i.e. the cells in your tongue that are sensing that sugar. As you activate this receptor and it's triggering activity after activity after activity, eventually you exhaust the receptor. Again, I'm using terms which are extraordinarily loose. But for sake of this discussion... For the sake of this discussion, the receptor gets to a point where it undergoes a set of changes, chemical changes, where it now signals far less efficiently, or it

• 1:16:10Speaker 01

  even gets removed from the surface of the cell. And now what will happen is that the same amount of sugar will trigger far less of a response. And that is a huge side of this modulation. And then the next, I believe, is the integrated, again, loss of signaling that happens by continuous activation of the circuit at each of these different neural stations. You know, there is from the tongue to the ganglia, from the ganglia to the first station in the brainstem, a second station in the brainstem, to the thalamus, then to the cortex. So there are multiple steps that this signal is traveling.

• 1:16:54Speaker 01

  Now, you might say, "Why, if this is a labeled line, why do you need to have so many stations?" And that's because the taste system is so important to ensure that you get what you need to survive, that it has to be subjected to modulation by the internal state. And each of these nodes provides a new side to give it plasticity and modulation, not necessarily to change the way that something tastes, but to ensure that you consume more or less of, or differently of what you need. I'm going to give you one example of how the internal state changes the way the taste system works.

• 1:17:41Speaker 01

  It's very appetitive at low concentrations, and that's because we need it. It's our electrolyte balance requires salt. Every one of the neurons uses salt as the most important of the ions, you know, with potassium to ensure that you can transfer these electrical signals within and between neurons.

• 1:18:04Speaker 01

  But at high concentrations, let's say ocean water, is incredibly aversive. And we all know this because we've gone to the ocean and then when you get it in your mouth, it's not that great. However, if I salt deprive you, and we can do this in experimental models quite readily,

• 1:18:27Speaker 01

  now this incredibly high concentration of salt, one molar sodium chloride, becomes amazingly appetitive and attractive. What's going on in here? Your tongue is telling you, "This is horrible." But your brain is telling you, "I don't care, you need it."

• 1:18:49Speaker 01

  And this is what we call the modulation of the taste system by the internal state.

• 1:18:57Andrew D. Huberman?

  And presumably, if one is hungry enough, even uni will taste good.

• 1:19:00Speaker 01

  You hit it right on the money. No, no, this is exactly correct. Or if you're thirsty and hungry,

• 1:19:09Speaker 01

  you suppress hunger, so that you don't waste water molecules in digesting food. Why? Because if you're thirsty and you have no water, you will die within a week or so.

• 1:19:24Speaker 01

  But you can go on a hunger strike as long as you have water for months, because you're gonna eat up all your energy reserves. Water is a different story. So you could see that there are multiple layers at which...

• 1:19:41Speaker 01

  The taste system that guides, you know, our drive and our motivation to consume the nutrients we need has to be modulated in response to the internal state. And of course, internal state itself has to be modulated by the external world. And so that, I think, is a reason why what could otherwise would have been an incredibly simple system from the tongue to the cortex in one just wire. It's not. Because you have to ensure that, you know, each step, you give the system that level of flexibility, or what we call in neuroscience plasticity.

• 1:20:23Andrew D. Huberman?

  I think we're headed into the gut.

• 1:20:26Speaker 01

  All right.

• 1:20:26Andrew D. Huberman?

  But I have a question that has just been on my mind for a bit now. Because I was drinking this water, and it has essentially no taste.

• 1:20:36Speaker 01

  Yes.

• 1:20:37Andrew D. Huberman?

  Is there any kind of signal for the absence of taste, despite having something in the mouth? And here is why I ask. What I'm thinking about is saliva. And while it's true that if I eat a lot of very highly palatable foods, that does change how I experience more bland foods. I must confess, when I eat a lot of these highly processed foods, I don't particularly like them. I tend to crave healthier foods, but that's probably for contextual reasons about nutrients, et cetera. But I could imagine an experiment where...

• 1:21:10Speaker 01

  Is there a taste of no taste?

• 1:21:11Andrew D. Huberman?

  Right. Is there a taste of no taste? Because in the visual system, there is.

• 1:21:14Speaker 01

  Mm-hmm.

• 1:21:15Andrew D. Huberman?

  Right? You close the eyes and you start getting increases in activity in the visual system as opposed to decreases, which often surprises people. But there are reasons for that. Because everything is about signal to noise, signal to background, and...

• 1:21:27Speaker 01

  It's a good question. I can tell you that most of our work is trying to focus on how the taste system works, not how it doesn't work.

• 1:21:36Andrew D. Huberman?

  Well, but I know you're being playful, and I knew when inviting you here today, I was setting myself up for I actually on a different

• 1:21:44Speaker 01

  We're trying to learn things.

• 1:21:45Andrew D. Huberman?

  Yeah, I know.

• 1:21:46Speaker 01

  However.

• 1:21:46Andrew D. Huberman?

  All right, listen, I was weaned in this system of, and I'll say it here for the second Actually, I recorded a podcast recently with a very prominent podcast, the Lex Friedman podcast, and I made reference to the so-called New York Neuroscience Mafia. I won't say whether or not we are sitting in the presence of the New York Neuroscience Mafia member, but in any event, I know the sorts of ribbing that they provide. For those listening, this is the kind of hazing that happens, benevolent hazing in academia. I'm the target.

• 1:22:17Speaker 01

  Of course.

• 1:22:19Andrew D. Huberman?

  It's a sign of love.

• 1:22:20Speaker 01

  Exactly.

• 1:22:20Andrew D. Huberman?

  He's gonna tell me that.

• 1:22:21Speaker 01

  And it's always about the science in the end.

• 1:22:24Andrew D. Huberman?

  Right.

• 1:22:25Speaker 01

  But it's an interesting question. Look, I don't know the answer, and I don't even know how I would explore it in a way that you will rigorously teach me.

• 1:22:43Speaker 01

  But

• 1:22:46Andrew D. Huberman?

  Let me tell you why I'm asking, and then I'll offer an experiment.

• 1:22:48Speaker 01

  Yes.

• 1:22:49Andrew D. Huberman?

  That I'd love to see someone in here.

• 1:22:50Speaker 01

  Excellent.

• 1:22:51Andrew D. Huberman?

  I'm thinking about saliva.

• 1:22:53Speaker 01

  Yes.

• 1:22:53Andrew D. Huberman?

  Which itself

• 1:22:54Speaker 01

  No, no, but that we know, that we can figure it out.

• 1:22:56Andrew D. Huberman?

  But the question is whether or not the saliva in a fed state is distinct from the saliva in an unfed state, such that it modulates

• 1:23:07Speaker 01

  It's not.

• 1:23:08Andrew D. Huberman?

  The sensitivity of the receptors.

• 1:23:09Speaker 01

  That experiment has been done, no.

• 1:23:10Andrew D. Huberman?

  It has been done. And so the answer is no.

• 1:23:12Speaker 01

  It's not, yeah, and the way you could do the experiment is because we use artificial saliva.

• 1:23:17Andrew D. Huberman?

  There's such a thing? I know there's artificial tears, but

• 1:23:21Speaker 01

  No, no, we, I don't mean that you go to Walgreens and you get, I mean, we in my laboratory, we know the composition of saliva, and so you can make such a thing. And, and, and, and you can take, you know, taste salts in culture, or in a tongue where you wash it out of, and then you can apply artificial saliva, and what happens is that the system is being engineered to desensitize

• 1:23:48Speaker 01

  To become agnostic, for saliva to become invisible. And there is no difference on the state of the animal.

• 1:23:59Andrew D. Huberman?

  Great. Well, this is the reason to do experiments.

• 1:24:01Speaker 01

  Yeah, absolutely.

• 1:24:02Andrew D. Huberman?

  So it doesn't defeat any grand hypothesis. It's just a pure curiosity. So...

• 1:24:07Speaker 01

  You know that curiosity killed the cat, yeah?

• 1:24:09Andrew D. Huberman?

  I do.

• 1:24:13Andrew D. Huberman?

  But saves the career of the scientist. Every single time.

• 1:24:16Speaker 01

  That's what drives us, absolutely.

• 1:24:18Andrew D. Huberman?

  Every single time.

• 1:24:19Speaker 01

  It's the story of our lives.

• 1:24:20Andrew D. Huberman?

  Exactly. Okay, so if it's not saliva, and apparently it is not,

• 1:24:26Andrew D. Huberman?

  what about internal state? And what aspects of this, the internal milieu are relevant? Because there's autonomic, there's asleep and awake, there's stress. One of the questions that I got from hundreds of people when I solicited questions in advance to this episode was, "Why do I crave sugar when I'm stressed?", for instance? And that could be contextual, but what are the basic elements?

• 1:24:48Speaker 01

  Because it makes us feel good, by the way. We'll get to that. That's the answer.

• 1:24:52Andrew D. Huberman?

  Sude.

• 1:24:52Speaker 01

  It activates what I'm going to generically refer to as reward-pleasure centers in a way that dramatically changes our internal state. This is, you know, why do we eat a gallon of ice cream when we're very depressed?

• 1:25:13Speaker 01

  In fact, this is a good segue to go into this entirely different world

• 1:25:20Speaker 01

  of the body telling your brain

• 1:25:25Speaker 01

  what you need in important things like sugar and fat. Okay, but anyways, go ahead. You were going to ask something.

• 1:25:33Andrew D. Huberman?

  Well, no, I would like to discuss the most basic elements of internal state. In particular, the ones that are below our conscious detection. And this is a, of course, is a segue into this incredible landscape, which is the gut-brain axis, which I think 15 years ago was almost a, maybe it was a couple of posters at a meeting. And then now, I believe, you and others, there are companies, there have companies, there are active research programs, and beautiful work. Maybe you could describe some of that work that you and others have been involved in? A lot of the listeners of this podcast will have heard of the gut-brain axis,

• 1:26:18Andrew D. Huberman?

  and there are a lot of misconceptions about the gut-brain axis. Many people think that this means that we think with our stomach because of the quote-unquote "gut feeling"

• 1:26:27Speaker 01

  Yes.

• 1:26:27Andrew D. Huberman?

  aspect, but I'd love you to talk about the aspects of gut-brain signaling that drive our, or change our perceptions and behaviors that are completely beneath our awareness.

• 1:26:37Speaker 01

  Yes, excellent. So let me begin maybe by stating that, you know, the brain needs to monitor the state of every one of our organs. Organs, it has to do it. This is the only way that the brain can ensure that every one of those organs are working together in a way that we have healthy physiology. Now, this monitoring of the brain has been known for a long time, but I think what hadn't been fully appreciated, that this is a two-way highway,

• 1:27:19Speaker 01

  where the brain is not only monitoring, but is now modulating back what the body needs to do. And that includes all the way from monitoring the frequency of heartbeats and the way that inspiration and aspirations in the breathing cycle operate, to what happens when you ingest sugar and fat. Now, let me give you an example, again, of of how the brain can take

• 1:28:00Speaker 01

  what we would refer to contextual associations, and transform it into incredible changes in physiology and metabolism. Remember Pavlov? So Pavlov, in his classical experiments in conditioning, you know, associative conditioning, he would take a bell, it would ring the bell every time he was going to feed the dog. And eventually, the dog learned to associate the ringing of the bell with food coming.

• 1:28:35Speaker 01

  Now, the first incredible finding he made is the fact that the dog now, in the presence of the bell alone, will start to salivate. And we will call that, you know, neurologically speaking, an anticipatory response. Okay, I could understand it. I get it. You know, neurons in the brain that form that association now represent food is coming, and they're sending a signal to motor neurons to go into your salivary glands to squeeze them, so you release, you know, saliva because you know food is coming.

• 1:29:15Speaker 01

  But what's even more remarkable is that those animals are also releasing insulin in response to a bell. Okay. This illustrates one part of this two-way highway, the highway going down. Somehow, the brain created these associations, and there are neurons in your brain now that know food is coming, and send a signal somehow all the way down to your pancreas, that now it says, "Release insulin because sugar is coming down." All right. This goes back to the magic of the brain. It's a never-ending source of both joy and intrigue.

• 1:29:59Speaker 01

  How the hell do they do this? Okay. I mean, the neurons, eh?

• 1:30:03Andrew D. Huberman?

  I share your delight and fascination. There's not a day, or a lecture, or some talks are better than others, or a talk where I don't sit back and just think, "It's absolutely amazing."

• 1:30:18Speaker 01

  How?

• 1:30:19Andrew D. Huberman?

  It's amazing.

• 1:30:20Speaker 01

  Now, over the past, I don't know, dozen years, and with great force over the last five years.

• 1:30:29Speaker 01

  Now, the main highway that is communicating the state of the body with the brain has been uncovered as being what we now refer to as the gut-brain axis. And the highway is a specific bundle of nerves, you know, which emerge from the vagal ganglia, the nodos ganglia. And so it's the vagus nerve that is innovating the majority of the organs in your body. It's monitoring their function, sending a signal to the brain, and now the brain going back down and saying, "This is going alright, do this, or this is not going so well, do that."

• 1:31:14Andrew D. Huberman?

  And I should point out, as you well know, every organ, spleen, pancreas, lungs...

• 1:31:21Speaker 01

  They all must be monitored. In fact, you know, I now, I have no doubt that diseases that we have normally associated with metabolism, physiology, and even immunity are likely to emerge as diseases, conditions, states of the brain. I don't think obesity is a disease of metabolism. I believe obesity is a disease of brain circuits.

• 1:31:55Andrew D. Huberman?

  I do as well.

• 1:31:56Speaker 01

  And so this view that we have, you know, been working on for the longest time, because, you know, the molecules that we're dealing with are in the body, not in the head, you know, led us to, you know, to view, of course, these issues and problems as being one of metabolism, physiology, and so forth. They remain to be the carriers of the ultimate signal. But the brain ultimately appears to be the conductor of this orchestra of physiology and metabolism. Alright, now, let's go to the gut-brain and sugar.

• 1:32:36Speaker 01

  May we?

• 1:32:37Andrew D. Huberman?

  Please, please. No, I mean, the the vagus nerve has in popular culture has been kind of converted into this single meaning of calming pathways. Mostly because I actually have to tip my hat to the yogic community was among the first to talk about Vegas on and on and on. There are calming pathways or, you know, so-called parasympathetic pathways within the Vegas. But I think that the more we learn about the Vegas, the more it seems like an entire set of neural connections as opposed to one nerve. I just wanted to just mention that because I think a lot of people have heard about the Vegas.

• 1:33:21Andrew D. Huberman?

  Turns out experimentally in the laboratory, many neuroscientists will stimulate the Vegas to create states of alertness and arousal when animals or even people, believe it or not, are close to dying or going into coma. Stimulation of the Vegas is one of the ways to wake up the brain, counter to the idea that it's just this way of calming oneself down.

• 1:33:41Speaker 01

  And also, of course, I mean, one has to be cautious there in that. So the the the vagus nerve is made out of many thousands of fibers, you know, individual fibers that make this gigantic bundle. And it's likely, as we're speaking, that each of these fibers carries a slightly different meaning. They're not necessarily one by one, maybe five fibers, 10 fibers, 22. But they carry meaning that's associated with their specific task. This group of fibers is telling the brain about the state of your heart.

• 1:34:23Speaker 01

  This group of fiber is telling the brain about the state of your gut. This is telling your brain about its nutritional state. This, your pancreas. This, your lungs. And they are, again, to make the same simple example, the keys of this piano. Yes, you're right, there is a lot of data showing that activating the entire vagal bundle has.

• 1:34:58Speaker 01

  Very meaningful effects in a wide range of conditions. In fact, it's being used to treat untractable depression. Those stimulator.

• 1:35:11Speaker 01

  Epileptic seizures.

• 1:35:14Speaker 01

  But again, there are thousands of fibers carrying different functions. So to some degree, you know, this is like

• 1:35:26Speaker 01

  turning the lights on the stadium because you need to illuminate where you lost your keys under your seat. Yet 10,000 bulbs of 1,000 watts each have just come on.

• 1:35:46Speaker 01

  Only one of these is pointing toward. And so I'm lucky enough that one of them happened to point to my side.

• 1:35:56Speaker 01

  So here you activate the bundle of thousands of fibers. I'm lucky enough that some of those happen to do something to make a meaningful difference in depression or to make a meaningful difference in epileptics. But it should not be misconstrued as arguing that this broad activation

• 1:36:20Speaker 01

  has any type of selectivity or specificity. We're just lucky enough that among all the things that have been done, some of those happen to change the biology of these processes. Now, the reason this is relevant because the magic of this gut-brain axis

• 1:36:41Speaker 01

  is the fact that you have these thousands of fibers really doing different functions. And our goal, and along with many other great, you know, scientists.

• 1:36:56Speaker 01

  Including Steve Lieberleis, that started a lot of, you know, this molecular dissection on this vagal gut-brain communication line at Harvard.

• 1:37:09Speaker 01

  He's trying to uncover what are each of those lines doing? What are each of those keys of this piano playing?

• 1:37:18Andrew D. Huberman?

  What's the latest there? Just as a brief update, I know Stephen Lieberleis, I think I was there when he got his Howard Hughes and I did not. So that was fun. Always great to get beat by excellent people.

• 1:37:29Speaker 01

  First of all, I'm happy you didn't because that way you can focus on this amazing podcast.

• 1:37:35Andrew D. Huberman?

  Thank you. That's very gracious of you. It's always feels better, if not good, to get beat out by excellent people. Stephen is second to none. And he is defining, as you said, the molecular constituents of different elements of these many, many fibers. Is there an update there? Are they finding multiple parallel pathways?

• 1:37:56Speaker 01

  They are, they are. Some that control heartbeat, some that control the respiratory cycle, some that might be involved in a gastric movement. You know, this notion that you're full and you feel full in part because your gut gets distended, your stomach, for example. And then there are little sensors that are reading that and telling the brain, you're full.

• 1:38:26Andrew D. Huberman?

  So the textbooks will soon change on the basis of the Lieberleis and other work.

• 1:38:31Speaker 01

  In essence, I think we are learning enough about these lines.

• 1:38:37Speaker 01

  That could really help put together this holistic view of how the brain, it's truly changing body physiology, metabolism and immunity. The part that hasn't been yet developed and that it needs a fair amount of work, but it's an exciting, thrilling, you know, journey of discovery is how the signal comes back to now change that biology. You know, the example I gave you before with Pavlov's dog.

• 1:39:14Speaker 01

  All right, I figure out, you know, how the association created this link between the bell. But then how does the brain tell the pancreas? To release in the right amount of insulin. Okay, so tell me, tell me. Let me tell you

• 1:39:33Speaker 01

  about the gut-brain axis and our insatiable appetite for sugar and fat. Insatiable for sugar and quenchable for fat.

• 1:39:49Speaker 01

  And this is a story about the fundamental difference between liking and wanting.

• 1:40:00Speaker 01

  Liking sugar

• 1:40:04Speaker 01

  is the function of the taste system.

• 1:40:09Speaker 01

  And it's not really liking sugar, it's liking sweet.

• 1:40:15Speaker 01

  Wanting sugar, our never-ending appetite for sugar, is the story of the gut-brain axis. Liking versus wanting. And this work is work of my own laboratory, you know, that began long ago when we discovered the sweet receptors.

• 1:40:40Speaker 01

  And you can now engineer mice that lack these receptors.

• 1:40:46Speaker 01

  So, in essence, these animals will be unable to taste sweet.

• 1:40:52Speaker 01

  A life without sweetness, how horrible. And if you give a normal mouse a bottle containing sweet, and we're gonna put either sugar or an artificial sweetener. All right, they both are sweet. They have slightly different tastes, but that's simply because artificial sweeteners have some off-tastes. But as far as the sweet receptor is concerned, they both activate the same receptor, trigger the same signal.

• 1:41:25Speaker 01

  And if you give an animal an option of a bottle containing sugar or a sweetener versus water, this animal will drink ten to one from the bottle containing sweet. That's the taste system. The animal goes, samples each one, leaks a couple of leaks, and then says, uh, uh, that's the one I want because it's appetitive and because I love it.

• 1:41:46Andrew D. Huberman?

  So it prefers sugar to artificial sweetener?

• 1:41:49Speaker 01

  No, no, no, no. In this experiment, this experiment, I'm gonna put only sweet in one bottle, and it could be either sugar or artificial sweetener, it doesn't matter which one. Okay, we're gonna do the next experiment where we separate those two. For now, it's sweet versus water.

• 1:42:06Andrew D. Huberman?

  Okay.

• 1:42:07Speaker 01

  And sweet means sweet, not sugar. Sweet means anything that tastes sweet, all right? And sugar is one example, and Splenda is another example.

• 1:42:18Andrew D. Huberman?

  Aspartame, monk fruit, stevia, doesn't matter.

• 1:42:23Speaker 01

  Yeah, I mean, there's some that only humans can taste, mice cannot taste, because their receptors between humans and mice are different. But we have put the human receptor into mice. We engineer mice, and we completely humanize this mouse's taste world, all right? But for the purpose of this conversation, we're only comparing sweet versus water. An option, my goodness, they will leak to know from the sweet side, ten to one at least versus the water. Make sense? All right. Now, we're gonna take the mice, and we're gonna genetically engineer it

• 1:43:07Speaker 01

  to remove the sweet receptors. So these mice no longer have in their oral cavity any sensors that can detect sweetness, be that sugar molecule, be it an artificial sweetener, be it anything else that tastes sweet.

• 1:43:23Speaker 01

  And if you give this mice an option between sweet versus water, sugar versus water, artificial sugar versus water, it will drink equally well from both because it cannot tell them apart. Because it doesn't have the receptors for sweet, so that sweet bottle tastes just like water.

• 1:43:41Speaker 01

  Make sense? Makes sense. Very good. Now, we're gonna do the experiment with sugar. From now on, let's focus on sugar. So I'm gonna give a mouse now sugar versus water. Normal mouse will drink from the sugar, sugar, sugar, sugar, very little from the water. Knock out the sweet receptors, eliminate them. Mouse can no longer tell them apart, and it will drink from both.

• 1:44:08Speaker 01

  But if I keep the mouse in that cage for the next forty-eight hours,

• 1:44:15Speaker 01

  something extraordinary happens when I come forty-eight hours later, and I see what the mouse is leaking or drinking from. The mouse is drinking almost exclusively from the sugar bottle. How could this be? It cannot taste it. Doesn't have sweet receptors.

• 1:44:36Speaker 01

  During those forty-eight hours, the mouse learned that there is something in that bottle that makes me feel good. And that is the bottle I want to consume. Now, how does the mouse identify that bottle? It does so by using other sensory features. The smell of the bottle, the texture of the solution inside, sugar, the high concentrations is kind of goopy.

• 1:45:07Speaker 01

  The sideness in which the bottle is in the cage, it doesn't matter what, but the mouse realized there is something there that makes me feel good, and that's what I want. And that is the fundamental basis of our unquenchable desire and our craving for sugar, and is mediated by the gut-brain axis.

• 1:45:35Speaker 01

  The first clue is that it takes a long time to develop,

• 1:45:39Speaker 01

  immediately suggesting a post-ingestive effect.

• 1:45:45Speaker 01

  So we reason if this is true and it's the gut-brain axis that's driving sugar preference, then there should be a group of neurons in the brain that are responding to post-ingestive sugar. And lo and behold, we identify a group of neurons in the brain that does this, and these neurons receive their input directly from the gut-brain axis.

• 1:46:12Andrew D. Huberman?

  From other neurons.

• 1:46:15Speaker 01

  You got it. And so what's happening is that sugar is recognized normally by the tongue, activates an appetitive response. Now you ingest it, and now it activates a selective group of cells in your intestines that now send a signal to the brain via the vagal ganglia that says, "I got what I need." The tongue doesn't know that you got what you need. It only knows that you tasted it. This knows that it got to the point that it's going to be used, which is the gut.

• 1:46:56Speaker 01

  And now it sends the signal to now reinforce the consumption of this thing because this is the one that I needed, sugar.

• 1:47:07Andrew D. Huberman?

  Source of energy. And are these neurons in the gut?

• 1:47:11Speaker 01

  So these are not neurons in the gut. So these are gut cells that recognize the sugar molecule.

• 1:47:16Andrew D. Huberman?

  I see.

• 1:47:17Speaker 01

  Send a signal, and that signal is received by the vagal neuron directly.

• 1:47:21Andrew D. Huberman?

  Got it.

• 1:47:22Speaker 01

  And it sends a signal through the gut-brain axis to the cell bodies of these neurons in the vagal ganglia, and from there to the brain stem to now trigger the preference for sugar.

• 1:47:37Andrew D. Huberman?

  Two questions. One, you mentioned that these cells that detect sugar within the gut are actually within the intestine? You didn't say stomach, which surprised me. I always think gut as stomach, but of course intestine.

• 1:47:50Speaker 01

  Their intestine, because that's where all the absorption happens. So you want the signal, you see, you want the brain to know that you had successful ingestion and breakdown of whatever you consume into the building blocks of life.

• 1:48:06Speaker 01

  And you know, glucose, amino acids, fatty. And so you wanna make sure that once they are in the form that intestines can now absorb them, is where you get the signal back saying, this is what I want. Okay? Now, let me just take it one step further. And this now, sugar molecules activates this unique gut-brain circuit that now drives the development of our preference for sugar. Now, a key element of this circuit is that the sensors in the gut that recognize the sugar

• 1:48:48Speaker 01

  do not recognize artificial sweeteners at all.

• 1:48:52Andrew D. Huberman?

  Right, because their nutrient value is uncoupled from the taste.

• 1:48:58Speaker 01

  Generically speaking, one can make that, but it's because it's a very different type of receptor.

• 1:49:03Andrew D. Huberman?

  I see.

• 1:49:04Speaker 01

  Turns out that's not the tongue receptors being used in the gut. It's a completely different molecule that only recognizes the glucose molecule, not artificial sweeteners. This has a profound impact on the effect of ultimately artificial sweeteners in curbing our appetite, our craving, our insatiable desire for sugar. Since they don't activate the gut-brain axis, they'll never satisfy the craving for sugar like sugar does. And the reason I believe

• 1:49:45Speaker 01

  that artificial sweeteners have failed in the market to curb our appetite, our need, our desire for sugar, is because they beautifully work on the tongue.

• 1:50:01Speaker 01

  The liking to recognize sweet versus non-sweet. But they failed to activate the key sensors in the gut that now inform the brain. You got sugar, no need to crave anymore.

• 1:50:22Andrew D. Huberman?

  So the issue of wanting, can we relate that to a particular set of neurochemicals upstream? So the pathway is, so glucose is activating the cells in the gut that through the vagus that's communicated through the presumably the nodos ganglion and up into the brainstem.

• 1:50:40Speaker 01

  Very good. And from there, where does it go?

• 1:50:42Andrew D. Huberman?

  Yeah, where is it going? What is the substrate of wanting? I, you know, of course, I think molecules like dopamine craving, there's a book even called The Molecule of More, et cetera, et cetera. Dopamine is a very diabolical molecule, as you know, because it evokes both a sense of pleasure-ish, but also a sense of desiring more, of craving. So if I understand you correctly, artificial sweeteners are, and I agree, are failing as a means to satisfy sugar craving at the level of nutrient sensing. And yet, if we trigger this true sugar-evoked wanting pathway too much, and we've all experienced

• 1:51:26Andrew D. Huberman?

  this, then we eat sugar and we find ourselves wanting more and more sugar. Now, that could also be insulin dysregulation, but can we uncouple those?

• 1:51:35Speaker 01

  Yeah, I mean, look. We have a mega problem with overconsumption of sugar and fat. We're facing a unique time in our evolution where diseases of malnutrition are due to overnutrition. I mean, how nuts is that? I mean, historically, diseases of malnutrition have always been linked to undernutrition. And so we need to come up with strategies that can meaningfully change.

• 1:52:20Speaker 01

  The activation of these circuits that control our wanting, certainly in the populations at risk.

• 1:52:33Speaker 01

  And this gut-brain circuit that ultimately, you know, it's the lines of communication that are informing the brain, the presence of intestinal sugar in this example. It's a very important target in the way we think about, is there a way that we can meaningfully modulate these circuits? So I make your brain think

• 1:53:01Speaker 01

  that you got satisfied with sugar even though I'm not giving you sugar.

• 1:53:07Andrew D. Huberman?

  So that immediately raises the question, are the receptors for glucose in these gut cells susceptible to other things that are healthier for us?

• 1:53:17Speaker 01

  That's very good. Excellent idea. And I think an important goal will be to come up with a strategy and identify those very means that allow us to modulate the circuits in a way that certainly for all of those where this is a big issue, it can really have a, you know, dramatic impact in improving human health.

• 1:53:48Andrew D. Huberman?

  I could be wrong about this and I'm happy to be wrong. I'm often wrong and told I'm wrong. That we have cells within our gut that don't just sense sugar, glucose, to be specific, but also cells within our gut that sense amino acids and fatty acids. I could imagine a scenario where one could train themselves to feel immense amounts of satiety from the consumption of foods that are rich in essential fatty acids, amino acids, perhaps less caloric or less insulin dysregulating than sugar.

• 1:54:27Andrew D. Huberman?

  I'll use myself as an example. I've always enjoyed sweets, but in the last few years, for some reason, I've started to lose my appetite for them, probably because I just don't eat them anymore. At first, that took some restriction. Now I just don't even think about it.

• 1:54:41Speaker 01

  Yeah, and you're not reinforcing the circuits. And so you, in essence, are removing yourself. But you tend to be the exception. You know, we have a huge, a huge, incredibly large number of people that are being continuously exposed to highly processed foods.

• 1:55:02Andrew D. Huberman?

  And hidden, so-called hidden sugars.

• 1:55:05Speaker 01

  They don't even have to be hidden. You know, it's right there.

• 1:55:09Andrew D. Huberman?

  Hiding in plain sight. Yeah, I agree. So much is made of hidden sugars that we often overlook that they are, there are also the overt sugars.

• 1:55:18Speaker 01

  Yeah, I mean, we can have a long discussion on the importance of coming up with strategies, you know, that could meaningfully change public health when it comes to nutrition.

• 1:55:33Speaker 01

  But I want to just go back to the notion of, you know, these brain centers that are ultimately the ones that are being activated by these essential nutrients. So, sugar, fat, and amino acids are building blocks of our diets. And this is across all animal species. So it's not unreasonable then to assume that dedicated brain circuits would have evolved to ensure their recognition, their ingestion, and the reinforcement that that is what

• 1:56:15Speaker 01

  I need. And indeed, you know, animals evolved this tool.

• 1:56:24Speaker 01

  Systems. One is the taste system. That allows you to recognize them. And trigger this predetermined, hardwired, immediate responses, yes? Oh my goodness, this tastes so good, it's so sweet. I personally have a sweet tooth, may I add? And, you know, oh my god, this is so delicious, it's fatty. Or umami, recognizing amino acids. So that's the liking pathway, yeah?

• 1:56:54Speaker 01

  But in the wisdom of evolution.

• 1:56:59Speaker 01

  That's good, but doesn't quite do it. You want to make sure that these things get to the place where they're needed. And they're not needed in your tongue.

• 1:57:09Speaker 01

  They are needed in your intestines, where they are going to be absorbed. As the nutrients that will support life. And the brain wants to know this. And he wants to know it in a way that he can now form the association between. That that I just tasted.

• 1:57:33Speaker 01

  Is what God worried needs to be. And it makes me feel good. And so now, next time that I have to choose. What should I eat? That association. Now guides me to, that's the one I want. I want that fruit, not that fruit. I want those leaves, not those leaves. Because these are the ones that activate the right circuits. That ensure that the right nutrients got to the right place and told the brain. This is what I want and need.

• 1:58:12Speaker 01

  Are we on?

• 1:58:13Andrew D. Huberman?

  We're on. One thing that intrigues me and puzzles me.

• 1:58:16Speaker 01

  Yes.

• 1:58:17Andrew D. Huberman?

  Is that this effect took a couple of days, at least in mice.

• 1:58:21Speaker 01

  Yes.

• 1:58:22Andrew D. Huberman?

  And the sensation, ah, sorry, the perception of taste.

• 1:58:25Speaker 01

  Is immediate.

• 1:58:26Andrew D. Huberman?

  Is immediate. And yet, this is a slow system and so. In a beautiful way, but in a kind of mysterious way. The brain is able to couple the taste of a sweet drink. With the experience of nutrient extraction in the gut. Under a context where the mouse and the human is presumably ingesting other things, smelling other mice, smelling other people, that's incredible.

• 1:58:49Speaker 01

  Yeah, but you have to think of it not as as humans. Remember, we inherited the circuits of our ancestors. And they through evolutionary from their ancestors. And we haven't had that many, you know, years to have fundamentally changed in many of these hard-wired circuits. So forget as humans, let's look at animals in the wild, okay? Which is easier now to comprehend the logic.

• 1:59:22Speaker 01

  You know, why should this take a long time of continual reinforcement? Given that I can taste it in a second? You want to make sure that this source of sugar, for example, in the wild, is the best, is the richest, is the one where I get the most energy for the least amount of extraction, the least amount of work. I want to identify rich sources of sugar. And if the system simply responds immediately to the first sugar that gets to your gut,

• 2:00:03Speaker 01

  you're going to form the association with those sources of food, which are not the ones that you should be eaten from.

• 2:00:12Andrew D. Huberman?

  Don't fall in love with the first person you encounter.

• 2:00:14Speaker 01

  Oh, my goodness, exactly. And so evolutionarily, by having the taste system giving you the immediate recognition, but then by forcing this gut-brain axis to reinforce it only when sustained, you know, repeated exposure has informed the brain, this is the one. You don't want to form the association before. And so, you know, when we remove it from the context of, you know, we just go to, you know, the supermarket. We're not hunting there in the wild where I need to form. And so what's happening is that...

• 2:00:59Speaker 01

  Highly processed foods are hijacking, you know, co-opting these circuits in a way that it would have never happened in nature. And then we not only find these things appetitive and palatable, but in addition, we are continuously reinforcing, you know, the wanting in a way that, "Oh, my God, this is so great. What do I feel like eating? Let me have more of this."

• 2:01:26Andrew D. Huberman?

  You've just forever changed the way that I think about supermarkets and restaurants. Their understanding, this fast signaling and this slower signaling, and the utility of having both makes me realize that supermarkets and restaurants are about the most unnatural thing for our system ever. Almost the equivalent of living in small villages with very few suitable mates versus online dating, for instance.

• 2:01:55Speaker 01

  Look, I'm not going to make a judgment call there because they do serve an important purpose.

• 2:01:59Andrew D. Huberman?

  I like restaurants, too.

• 2:02:00Speaker 01

  Yeah, but and so do supermarkets, thank God. I think they're not the culprits. Yeah, I think the culprits, of course, you know, are reliance on foods that are not necessarily healthy. Now, going back to the supermarket, the don't fall in love with the first, they need to work. You know, you take a tangerine and you take an extract of tangerine that you used to cook

• 2:02:44Speaker 01

  that spiked, let's say, with sugar. And you equalize them both where they both provide the same amount of calories. If you eat them both, they're going to have a very different effect in your gut-brain axis and your system. Once you make the extract and you process it and you add it processed sugar, you know, to use it now to cook, to add, to make a really sweet tangerine thing. Now, you're providing now a fully ready-to-use, broken-down source of sugar.

• 2:03:24Speaker 01

  In the tangerine, that sugar is mixed in the complexity of a whole set of other chemical components.

• 2:03:36Speaker 01

  Fiber, long chains of sugar molecules that need a huge amount of work by your stomach, your gut system, to break it down. So you're using a huge amount of energy to extract energy.

• 2:03:56Speaker 01

  And the balance, it's very different than when I take this processed, highly extracted tangerine. By the way, I use tangerines because I had a tangerine just before I came in.

• 2:04:09Andrew D. Huberman?

  Delicious. They are delicious.

• 2:04:12Speaker 01

  And so, and so this goes back to the issue of supermarkets. And so, to some degree, you know, A, given a choice, you don't want to eat processed, highly processed foods because everything's already been broken down for you. And so your system has no work.

• 2:04:32Speaker 01

  And so you are co-opting, hijacking these circuits in a way that they're being activated at a time scale that normally wouldn't happen.

• 2:04:41Andrew D. Huberman?

  This is why I often feel that, and I think a lot of data are now starting to support the idea that while indeed the laws of thermodynamics apply, calories ingested versus calories burned is a very real thing, right? That the

• 2:05:00Andrew D. Huberman?

  appetite for certain foods and the wanting and the liking are phenomena of the nervous system, brain and gut, as you've beautifully described. And that that changes over time depending on how we are receiving these nutrients.

• 2:05:17Speaker 01

  Absolutely. Look,

• 2:05:21Speaker 01

  we have a lot of work to do.

• 2:05:25Speaker 01

  I'm talking as a society. I'm not talking about you and I.

• 2:05:29Andrew D. Huberman?

  We also have a lot of work to do.

• 2:05:31Speaker 01

  Now. I think understanding the circuits is giving us important insights. And how ultimately, hopefully, we can improve human health and make a meaningful difference. Now, it's very easy to try to, you know, connect the dots, A to B, B to C, C to D. And I think there's a lot more complexity to it. But I do think that the lessons that are emerging out of understanding how the circuits operate can ultimately inform

• 2:06:14Speaker 01

  how we deal with our diets in a way that we avoid what we're facing now, you know, as a society. I mean, it's nuts that the overnutrition happens to be such a prevalent problem.

• 2:06:31Andrew D. Huberman?

  And I also think the training of people who are thinking about metabolic science and metabolic disease is largely divorced from the training of the neuroscientists, and vice versa. No one field is to blame. But I fully agree that the the brain is the key, or the nervous system, to be more accurate, is the, one of the key overlooked features.

• 2:06:52Speaker 01

  It's the arbitrary. Ultimately, it's the arbitrary of many of these pathways.

• 2:06:57Andrew D. Huberman?

  As a final question, and one which is simply to entertain my curiosity and the curiosity of the listeners. What is your absolute favorite food?

• 2:07:08Speaker 01

  Oh, my goodness.

• 2:07:12Andrew D. Huberman?

  Taste, I should say.

• 2:07:13Speaker 01

  Yes.

• 2:07:14Andrew D. Huberman?

  Taste, to distinguish between taste and the nutritive value or lack thereof.

• 2:07:19Speaker 01

  Look, we, unlike every other animal, and every other animal species, eat for the enjoyment of it.

• 2:07:30Speaker 01

  It doesn't happen in the wild. Most animals eat when they need to eat.

• 2:07:36Speaker 01

  Doesn't mean they don't enjoy it, but it's a completely different story, yeah?

• 2:07:44Speaker 01

  I have too many favorite foods because I enjoy the sensory experience. Rather than the food itself, to me, is the whole thing. It's from the present. Look, there've been these experiments done in psychophysics, eh? I'm gonna take a salad made out of 11 components.

• 2:08:04Speaker 01

  And I'm gonna mix them all up in a potpourri of greens and other things here. And in the other one, I'm gonna present it in a beautiful arrangement. And I'm gonna put it behind a glass cabinet, and I'm gonna sell them. And I'm gonna sell one for $2 and one for $8.

• 2:08:21Speaker 01

  Precisely the same ingredients, exactly the same amount of each. Ultimately, you're gonna mix them, they're all gonna be the same.

• 2:08:30Speaker 01

  And people will pay the $8 because, you know what? It evokes a different person.

• 2:08:39Speaker 01

  It gives you the feel that, "Oh, my goodness, I'm gonna enjoy that salad." So going back to, what is my favorite food? To me, eating is really a

• 2:08:54Speaker 01

  a sensory journey. I don't mean the everyday, "Let me have some, you know, chicken wings because I'm hungry."

• 2:09:05Speaker 01

  But every piece, I think, has an important, evoking sensory role. And so, you know, in terms of categories of food, you know, I grew up in Chile, yes, so meat is always been... But I eat it so seldom now. Is that right? Yeah, because, you know, I know that's not necessarily the whole of this thing. Red meat I'm talking about, eh? And so I, you know, I grew up eating it every day. I'm talking seven days a week, Chile and Argentina, you know, that's

• 2:09:49Speaker 01

  the mainstay of our diet, eh? Now, maybe I have red meat. I know, once every four weeks.

• 2:10:00Andrew D. Huberman?

  And you enjoy it.

• 2:10:01Speaker 01

  Oh, I love it. Part of it is because I haven't had it in four weeks, eh? But, you know, I, I love sushi, but I love the, the art of sushi. You know, the whole thing, you know, the way it's presented, it changes the way you taste it. I love ethnic food. In particular.

• 2:10:25Andrew D. Huberman?

  You're in the right place.

• 2:10:26Speaker 01

  You got it. That was the main reason I wanted to come to New York. No, I'm just kidding.

• 2:10:31Andrew D. Huberman?

  There's also that Columbia University that's.

• 2:10:34Speaker 01

  I came here because I wanted to be with, you know, people that are thinking about the brain the same way that I like to think, which, you know, can we solve this big problem? This big question.

• 2:10:45Andrew D. Huberman?

  And certainly you're making amazing strides in that direction. And I love your answer because it really brings together the many features of the circuitries and the phenomena we've been talking about today, which is that while it begins with sensation and perception, ultimately it's the context and that context is highly individual to person, place and time, and many, many other things. On behalf of myself, and certainly on behalf of all the listeners, I want to thank you, first of all, for the incredible work that you've been doing now for decades in vision, in taste, and in this bigger issue of how we perceive and experience life. It's truly pioneering and incredible work. And I feel quite lucky to have been on the sidelines, seeing this over the years

• 2:11:30Andrew D. Huberman?

  and hearing the talks and reading the countless beautiful papers. But also for your time today to come down here and talk to us about what drives you and the discoveries you've made. Thank you ever so much.

• 2:11:42Speaker 01

  It was great fun. Thank you for having me.

• 2:11:45Andrew D. Huberman?

  We'll do it again.

• 2:11:46Speaker 01

  Wish all.

• 2:11:48Andrew D. Huberman?

  Thank you for joining me today for my discussion about perception and in particular, the perception of taste with Dr. Charles Zucker. If you're learning from and/or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific, zero-cost way to support us. In addition, please subscribe to the podcast on Spotify and Apple. And on Spotify and Apple, you can leave us up to a five-star review. If you have feedback for us in terms of comments related to topics we've covered, or questions, or topics, or guests that you'd like us to cover on future episodes of the Huberman Lab Podcast, please put those in the comments section on YouTube. We do read all the comments. On today's episode of the Huberman Lab Podcast, we didn't talk about supplements, but on many previous episodes of the Huberman Lab Podcast, we talk about supplements that are useful for sleep, for

• 2:12:32Andrew D. Huberman?

  focus, for hormone support, and other aspects of mental health, physical health, and performance. If you're interested in some of those supplements, you can go to livemomentous.com/huberman to see the catalog of supplements that we've helped them formulate and that map directly onto specific protocols described on the Huberman Lab Podcast. Again, that's livemomentous.com/huberman. If you're not already following us on social media, we are Huberman Lab on Twitter and Huberman Lab on Instagram. And at both Twitter and Instagram, I cover science and science-related tools, some of which overlap with the content of the Huberman Lab Podcast, but much of which is distinct from the information contained in the Huberman Lab Podcast. We also have a newsletter in which we spell out protocols and some summaries from previous podcast

• 2:13:14Andrew D. Huberman?

  episodes. If you'd like to check those out, you can go to hubermanlab.com, go to the menu, and you'll find the Neural Network Newsletter. You can sign up for that newsletter simply by providing an email. It's completely zero cost. We have a very strict privacy policy. We do not share your email with anybody. Again, that's hubermanlab.com. Go to the menu and look for the Neural Network Newsletter. And if you'd like examples of previous newsletters, you'll also find those at hubermanlab.com. Once again, thank you for joining me today in my discussion with Dr. Charles Zuker about the biology of perception and the biology of the perception of taste in particular. I hope you found that discussion to be as enriching as I did. And last, but certainly not least, thank you for your interest in science.