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

Welcome to Huberman Lab Essentials, Welcome to Huberman Lab Essentials, where we revisit past episodes for the where we revisit past episodes for the where we revisit past episodes for the most potent and actionable science-based most potent and actionable science-based most potent and actionable science-based tools for mental health, physical tools for mental health, physical tools for mental health, physical health, and performance. health, and performance. health, and performance. I'm Andrew Huberman and I'm a professor I'm Andrew Huberman and I'm a professor I'm Andrew Huberman and I'm a professor of neurobiology and opthalmology at of neurobiology and opthalmology at of neurobiology and opthalmology at Stanford School of Medicine. And now for Stanford School of Medicine. And now for Stanford School of Medicine. And now for my discussion with Dr. Charles Zooker. my discussion with Dr. Charles Zooker. my discussion with Dr. Charles Zooker. Charles, thank you so much for joining Charles, thank you so much for joining Charles, thank you so much for joining me today. me today. me today. >> My pleasure. I want to ask you about >> My pleasure. I want to ask you about >> My pleasure. I want to ask you about many things related to taste and many things related to taste and many things related to taste and gustatory perception. But maybe to start gustatory perception. But maybe to start gustatory perception. But maybe to start off and because you've worked on a off and because you've worked on a off and because you've worked on a number of different topics in number of different topics in number of different topics in neuroscience, not just taste, how should neuroscience, not just taste, how should neuroscience, not just taste, how should the world and people think about the world and people think about the world and people think about perception? How it's different from perception? How it's different from perception? How it's different from sensation? And what leads to our sensation? And what leads to our sensation? And what leads to our experience of life in terms of vision, experience of life in terms of vision, experience of life in terms of vision, hearing, taste, etc. hearing, taste, etc. hearing, taste, etc. >> The world is made of real things. You >> The world is made of real things. You >> The world is made of real things. You know, this here is a glass know, this here is a glass know, this here is a glass and this is a chord and this is a and this is a chord and this is a and this is a chord and this is a microphone. But the brain is only made microphone. But the brain is only made microphone. But the brain is only made of neurons that only understand of neurons that only understand of neurons that only understand electrical signals. electrical signals. electrical signals. So how do you transform that reality So how do you transform that reality So how do you transform that reality into nothing but electrical signals that into nothing but electrical signals that into nothing but electrical signals that now need to represent the world now need to represent the world now need to represent the world and that process is we can is what we and that process is we can is what we and that process is we can is what we can operationally define as perception can operationally define as perception can operationally define as perception in the senses in the senses in the senses let's say alactory let's say alactory let's say alactory other taste vision you know we can very other taste vision you know we can very other taste vision you know we can very straightforwardly separate detection straightforwardly separate detection straightforwardly separate detection from perception. Detection is what from perception. Detection is what from perception. Detection is what happens when you take a sugar molecule, happens when you take a sugar molecule, happens when you take a sugar molecule, you put it in your tongue, and then a you put it in your tongue, and then a you put it in your tongue, and then a set of specific cells now sense that set of specific cells now sense that set of specific cells now sense that sugar molecule. That's detection. You sugar molecule. That's detection. You sugar molecule. That's detection. You haven't perceived anything yet. That is haven't perceived anything yet. That is haven't perceived anything yet. That is just your cells in your tongue just your cells in your tongue just your cells in your tongue interacting with this chemical. But now interacting with this chemical. But now interacting with this chemical. But now that cell gets activated and sends a that cell gets activated and sends a that cell gets activated and sends a signal to the brain and now detection signal to the brain and now detection signal to the brain and now detection gets transformed into perception. gets transformed into perception. gets transformed into perception. And he's trying to understand how that And he's trying to understand how that And he's trying to understand how that happens. That's been the happens. That's been the happens. That's been the the maniacal the maniacal the maniacal drive drive drive of my entire career in neuroscience. of my entire career in neuroscience. of my entire career in neuroscience. How does the brain ultimately transform How does the brain ultimately transform How does the brain ultimately transform detection into perception so that it can detection into perception so that it can detection into perception so that it can guide actions and behaviors? So if I guide actions and behaviors? So if I guide actions and behaviors? So if I want to begin to explore all of these want to begin to explore all of these want to begin to explore all of these things that the brain does, things that the brain does, things that the brain does, I felt I have to choose a sensory system I felt I have to choose a sensory system I felt I have to choose a sensory system that affords that affords that affords some degree of simplicity some degree of simplicity some degree of simplicity in the way that the input output in the way that the input output in the way that the input output relationships are put together. and in a relationships are put together. and in a relationships are put together. and in a way that still can be used to ask every way that still can be used to ask every way that still can be used to ask every one of these problems that the brain has one of these problems that the brain has one of these problems that the brain has to ultimately compute, encode, and to ultimately compute, encode, and to ultimately compute, encode, and decode. decode. decode. And what was remarkable about the taste And what was remarkable about the taste And what was remarkable about the taste system at the time that I began working system at the time that I began working system at the time that I began working on this on this on this is that nothing was known about the is that nothing was known about the is that nothing was known about the molecular basis of taste. molecular basis of taste. molecular basis of taste. You know, we knew that we could taste You know, we knew that we could taste You know, we knew that we could taste what has been usually defined as the b what has been usually defined as the b what has been usually defined as the b the five basic taste qualities. Sweet, the five basic taste qualities. Sweet, the five basic taste qualities. Sweet, sour, bitter, salty, and umami. Umami is sour, bitter, salty, and umami. Umami is sour, bitter, salty, and umami. Umami is a Japanese word that means yummy, a Japanese word that means yummy, a Japanese word that means yummy, delicious. delicious. delicious. And that's in nearly every animal And that's in nearly every animal And that's in nearly every animal species the taste of amino acids. and in species the taste of amino acids. and in species the taste of amino acids. and in humans is mostly associated with the humans is mostly associated with the humans is mostly associated with the taste of MSG monos sodium glutamate one taste of MSG monos sodium glutamate one taste of MSG monos sodium glutamate one amino acid in particular and so the amino acid in particular and so the amino acid in particular and so the beautiful thing of the system is that beautiful thing of the system is that beautiful thing of the system is that the lines of input are limited to five the lines of input are limited to five the lines of input are limited to five and each of them has a predetermined and each of them has a predetermined and each of them has a predetermined meaning you're born with that specific meaning you're born with that specific meaning you're born with that specific veilance value for each taste of sweet veilance value for each taste of sweet veilance value for each taste of sweet umami and low salt are attractive taste umami and low salt are attractive taste umami and low salt are attractive taste qualities. They evoke appetitive qualities. They evoke appetitive qualities. They evoke appetitive responses. I want to consume them. responses. I want to consume them. responses. I want to consume them. And bitter and sour And bitter and sour And bitter and sour are innately predetermined to be are innately predetermined to be are innately predetermined to be aversive. In the case of bitter, it's aversive. In the case of bitter, it's aversive. In the case of bitter, it's very easy to actually look at see them very easy to actually look at see them very easy to actually look at see them happening in animals because the first happening in animals because the first happening in animals because the first thing you do is you stop leaking. Then thing you do is you stop leaking. Then thing you do is you stop leaking. Then you put a unhappy face. Then you squint you put a unhappy face. Then you squint you put a unhappy face. Then you squint your eyes and then you start gagging. your eyes and then you start gagging. your eyes and then you start gagging. And that entire thing happens by the And that entire thing happens by the And that entire thing happens by the activation of a bitter molecule in a activation of a bitter molecule in a activation of a bitter molecule in a bitter sensing cell in your tongue. bitter sensing cell in your tongue. bitter sensing cell in your tongue. >> It's incredible. >> It's incredible. >> It's incredible. >> It's it's it's again the magic of the >> It's it's it's again the magic of the >> It's it's it's again the magic of the brain. You know how how it it's able to brain. You know how how it it's able to brain. You know how how it it's able to encode and decode these extraordinary encode and decode these extraordinary encode and decode these extraordinary actions and behaviors in response of actions and behaviors in response of actions and behaviors in response of nothing but a simple very you know nothing but a simple very you know nothing but a simple very you know unique sensory stimuli. This palette of unique sensory stimuli. This palette of unique sensory stimuli. This palette of five basic tastes accommodates all the five basic tastes accommodates all the five basic tastes accommodates all the dietary needs of the organism. Sweet to dietary needs of the organism. Sweet to dietary needs of the organism. Sweet to ensure that we get the right amount of ensure that we get the right amount of ensure that we get the right amount of energy. Umami to ensure that we get energy. Umami to ensure that we get energy. Umami to ensure that we get proteins, another essential nutrient. proteins, another essential nutrient. proteins, another essential nutrient. Salt, the three appetitive ones to Salt, the three appetitive ones to Salt, the three appetitive ones to ensure that we maintain our electrolyte ensure that we maintain our electrolyte ensure that we maintain our electrolyte balance. Bitter to prevent the ingestion balance. Bitter to prevent the ingestion balance. Bitter to prevent the ingestion of toxic nauseous chemicals. Nearly all of toxic nauseous chemicals. Nearly all of toxic nauseous chemicals. Nearly all bitter tasting, you know, things out in bitter tasting, you know, things out in bitter tasting, you know, things out in the wild are bad for you. And sour most the wild are bad for you. And sour most the wild are bad for you. And sour most likely to prevent ingestion of spoiled likely to prevent ingestion of spoiled likely to prevent ingestion of spoiled acid, acid, acid, fermented foods. And that's it. That is fermented foods. And that's it. That is fermented foods. And that's it. That is the pallet that we deal with. Now, of the pallet that we deal with. Now, of the pallet that we deal with. Now, of course, there's a difference between course, there's a difference between course, there's a difference between basic taste and flavor. Flavor is the basic taste and flavor. Flavor is the basic taste and flavor. Flavor is the whole experience. Flavor is the whole experience. Flavor is the whole experience. Flavor is the combination of multiple tastes coming combination of multiple tastes coming combination of multiple tastes coming together together with smell, with together together with smell, with together together with smell, with texture, with temperature, texture, with temperature, texture, with temperature, with the look of it that gives you what with the look of it that gives you what with the look of it that gives you what you and I would call the full sensory you and I would call the full sensory you and I would call the full sensory experience. But but we scientists need experience. But but we scientists need experience. But but we scientists need to reduce the the problem into its basic to reduce the the problem into its basic to reduce the the problem into its basic elements so we can begin to break it elements so we can begin to break it elements so we can begin to break it apart before we put it back together. So apart before we put it back together. So apart before we put it back together. So when we think about the sense of taste when we think about the sense of taste when we think about the sense of taste and we try to figure out how these lines and we try to figure out how these lines and we try to figure out how these lines of information go from your tongue to of information go from your tongue to of information go from your tongue to your brain and how they signal and how your brain and how they signal and how your brain and how they signal and how they get integrated and how they trigger they get integrated and how they trigger they get integrated and how they trigger all these different behaviors, we look all these different behaviors, we look all these different behaviors, we look at them as individual qualities. So we at them as individual qualities. So we at them as individual qualities. So we give the animals sweet or we give them a give the animals sweet or we give them a give the animals sweet or we give them a bitter, we give them sour. We avoid bitter, we give them sour. We avoid bitter, we give them sour. We avoid mixes. mixes. mixes. Think of it as lines of information. Think of it as lines of information. Think of it as lines of information. Just separate lines like the keys of a Just separate lines like the keys of a Just separate lines like the keys of a piano. Yeah. piano. Yeah. piano. Yeah. sweet sour beam. You play the key and sweet sour beam. You play the key and sweet sour beam. You play the key and you activate that one chord and that one you activate that one chord and that one you activate that one chord and that one chord in the case of a piano leads to a chord in the case of a piano leads to a chord in the case of a piano leads to a note you know a tune and in the case of note you know a tune and in the case of note you know a tune and in the case of taste lead to an action and a behavior. taste lead to an action and a behavior. taste lead to an action and a behavior. >> If you would describe the sequence of >> If you would describe the sequence of >> If you would describe the sequence of neural events leading to a perceptual neural events leading to a perceptual neural events leading to a perceptual event of taste. event of taste. event of taste. >> We have taste bats distributed in >> We have taste bats distributed in >> We have taste bats distributed in various parts of the tongue. So there is various parts of the tongue. So there is various parts of the tongue. So there is a map on the distribution of taste buds a map on the distribution of taste buds a map on the distribution of taste buds but each taste bud has around a 100 but each taste bud has around a 100 but each taste bud has around a 100 taste receptor cells and those taste taste receptor cells and those taste taste receptor cells and those taste receptor cells can be of five receptor cells can be of five receptor cells can be of five types. Yeah. Sweet, sour, bitter, salty types. Yeah. Sweet, sour, bitter, salty types. Yeah. Sweet, sour, bitter, salty or umami. And for the most part or umami. And for the most part or umami. And for the most part all taste buds have the representation all taste buds have the representation all taste buds have the representation of all five taste qualities. Now there's of all five taste qualities. Now there's of all five taste qualities. Now there's no question that there is a slight bias no question that there is a slight bias no question that there is a slight bias for some taste like bitter is for some taste like bitter is for some taste like bitter is particularly enriched at the very back particularly enriched at the very back particularly enriched at the very back of your tongue and there is a teological of your tongue and there is a teological of your tongue and there is a teological basis for that actually a biological basis for that actually a biological basis for that actually a biological basis for that. That's the last line of basis for that. That's the last line of basis for that. That's the last line of defense before you swallow something defense before you swallow something defense before you swallow something bad. bad. bad. And so let's make sure that the very And so let's make sure that the very And so let's make sure that the very back of your tongue has plenty of these back of your tongue has plenty of these back of your tongue has plenty of these bad news receptors bad news receptors bad news receptors so that if they get activated you can so that if they get activated you can so that if they get activated you can trigger a gagging reflex and get rid of trigger a gagging reflex and get rid of trigger a gagging reflex and get rid of this that otherwise may kill you. The this that otherwise may kill you. The this that otherwise may kill you. The important thing is that you know after important thing is that you know after important thing is that you know after the receptors for these five the the the receptors for these five the the the receptors for these five the the detectors the molecules that sense sweet detectors the molecules that sense sweet detectors the molecules that sense sweet sour be to mommy. These are receptors, sour be to mommy. These are receptors, sour be to mommy. These are receptors, proteins found on the surface of taste proteins found on the surface of taste proteins found on the surface of taste receptor cells that interact with these receptor cells that interact with these receptor cells that interact with these chemicals. And once they interact, then chemicals. And once they interact, then chemicals. And once they interact, then they trigger the cascade of events, they trigger the cascade of events, they trigger the cascade of events, biochemical events inside the cell that biochemical events inside the cell that biochemical events inside the cell that now sends an electrical signal that says now sends an electrical signal that says now sends an electrical signal that says there is sweet here or there is salt there is sweet here or there is salt there is sweet here or there is salt here. Let's compare and contrast sweet here. Let's compare and contrast sweet here. Let's compare and contrast sweet and bitter as we follow their lines from and bitter as we follow their lines from and bitter as we follow their lines from the tongue to the brain. So the first the tongue to the brain. So the first the tongue to the brain. So the first thing is that the two evoke thing is that the two evoke thing is that the two evoke diametrically opposed behaviors. If we diametrically opposed behaviors. If we diametrically opposed behaviors. If we have to come up with two sensory have to come up with two sensory have to come up with two sensory experience that represent polar experience that represent polar experience that represent polar opposites, it will be sweet and bitter. opposites, it will be sweet and bitter. opposites, it will be sweet and bitter. So then the signals, if we follow now So then the signals, if we follow now So then the signals, if we follow now these two lines, they're really like two these two lines, they're really like two these two lines, they're really like two separate keys at the two ends of this separate keys at the two ends of this separate keys at the two ends of this keyboard. And you press one key and you keyboard. And you press one key and you keyboard. And you press one key and you activate this chord. So you activate the activate this chord. So you activate the activate this chord. So you activate the sweet cells throughout your oral cavity sweet cells throughout your oral cavity sweet cells throughout your oral cavity and they all converge into a group of and they all converge into a group of and they all converge into a group of sweet neurons. In the next station which sweet neurons. In the next station which sweet neurons. In the next station which is still outside the brain is one of the is still outside the brain is one of the is still outside the brain is one of the taste ganglia. taste ganglia. taste ganglia. These are the neurons that intervate These are the neurons that intervate These are the neurons that intervate your tongue and the oral cavity. your tongue and the oral cavity. your tongue and the oral cavity. >> Where do they sit approximately? Are >> Where do they sit approximately? Are >> Where do they sit approximately? Are there there there >> around there? >> around there? >> around there? >> Yeah, right here around the the lymph >> Yeah, right here around the the lymph >> Yeah, right here around the the lymph nodes more or less. nodes more or less. nodes more or less. >> You got it. And there are two main >> You got it. And there are two main >> You got it. And there are two main ganglia ganglia ganglia that innervate the vast majority of all that innervate the vast majority of all that innervate the vast majority of all taste buds in the oral cavity. And then taste buds in the oral cavity. And then taste buds in the oral cavity. And then from there that sweet signal goes onto from there that sweet signal goes onto from there that sweet signal goes onto the brain stem. The brain stem is the the brain stem. The brain stem is the the brain stem. The brain stem is the entry of the body into the brain. And entry of the body into the brain. And entry of the body into the brain. And there are different areas of the brain there are different areas of the brain there are different areas of the brain stem and there are different groups of stem and there are different groups of stem and there are different groups of neurons in the brain stem. And there's a neurons in the brain stem. And there's a neurons in the brain stem. And there's a unique area in a unique topographically unique area in a unique topographically unique area in a unique topographically defined defined defined location location location in the rostral side of the brain stem in the rostral side of the brain stem in the rostral side of the brain stem that receives all of the taste input. that receives all of the taste input. that receives all of the taste input. >> A very dense area of the brain. >> A very dense area of the brain. >> A very dense area of the brain. >> A very rich area of the brain. Exactly. >> A very rich area of the brain. Exactly. >> A very rich area of the brain. Exactly. And from there, this sweet signal goes And from there, this sweet signal goes And from there, this sweet signal goes to this other area higher up on the to this other area higher up on the to this other area higher up on the brain stem. And then it goes through a brain stem. And then it goes through a brain stem. And then it goes through a number of stations where that sweet number of stations where that sweet number of stations where that sweet signal goes from sweet neuron to sweet signal goes from sweet neuron to sweet signal goes from sweet neuron to sweet neuron to sweet neuron to eventually get neuron to sweet neuron to eventually get neuron to sweet neuron to eventually get to your cortex. to your cortex. to your cortex. And once it gets to your taste cortex, And once it gets to your taste cortex, And once it gets to your taste cortex, that's where meaning is imposed into that's where meaning is imposed into that's where meaning is imposed into that signal. It's then this is what the that signal. It's then this is what the that signal. It's then this is what the data suggests that now you can identify data suggests that now you can identify data suggests that now you can identify this as a sweet stimuli this as a sweet stimuli this as a sweet stimuli >> and how quickly does that all happen? >> and how quickly does that all happen? >> and how quickly does that all happen? >> You know the time scale of the nervous >> You know the time scale of the nervous >> You know the time scale of the nervous system it's fast. Yeah. And system it's fast. Yeah. And system it's fast. Yeah. And >> within less than a second. >> within less than a second. >> within less than a second. >> Yeah. And and in fact we can demonstrate >> Yeah. And and in fact we can demonstrate >> Yeah. And and in fact we can demonstrate this because we can stick electrodes at this because we can stick electrodes at this because we can stick electrodes at each of these stations. You deliver the each of these stations. You deliver the each of these stations. You deliver the stimuli and within a fraction of a stimuli and within a fraction of a stimuli and within a fraction of a second you see now the response in this second you see now the response in this second you see now the response in this following stations. Now it gets to the following stations. Now it gets to the following stations. Now it gets to the cortex and now in there you impose cortex and now in there you impose cortex and now in there you impose meaning to that taste. There's an area meaning to that taste. There's an area meaning to that taste. There's an area of your brain that represents the taste of your brain that represents the taste of your brain that represents the taste of sweet in taste cortex and a different of sweet in taste cortex and a different of sweet in taste cortex and a different area that represents the taste of area that represents the taste of area that represents the taste of bitter. In essence, there is a bitter. In essence, there is a bitter. In essence, there is a topographic map of these taste qualities topographic map of these taste qualities topographic map of these taste qualities inside your brain. inside your brain. inside your brain. >> How much plasticity do you think there >> How much plasticity do you think there >> How much plasticity do you think there is there? And in particular across the is there? And in particular across the is there? And in particular across the lifespan because I think one of the most lifespan because I think one of the most lifespan because I think one of the most salient examples of this is that kids salient examples of this is that kids salient examples of this is that kids don't seem to like certain vegetables, don't seem to like certain vegetables, don't seem to like certain vegetables, but they all are hardwired to like sweet but they all are hardwired to like sweet but they all are hardwired to like sweet tastes. And yet you could also imagine tastes. And yet you could also imagine tastes. And yet you could also imagine that one of the reasons why they may that one of the reasons why they may that one of the reasons why they may eventually grow to incorporate eventually grow to incorporate eventually grow to incorporate vegetables is because of some knowledge vegetables is because of some knowledge vegetables is because of some knowledge that vegetables might be that vegetables might be that vegetables might be >> good for you, >> good for you, >> good for you, >> better for them. Is there a change in >> better for them. Is there a change in >> better for them. Is there a change in the receptors that can explain the the receptors that can explain the the receptors that can explain the transition from wanting to avoid transition from wanting to avoid transition from wanting to avoid vegetables to being willing to eat vegetables to being willing to eat vegetables to being willing to eat vegetables simply in childhood to to vegetables simply in childhood to to vegetables simply in childhood to to early development? early development? early development? >> It tastes we just told you that's you >> It tastes we just told you that's you >> It tastes we just told you that's you know predetermined hardwire but know predetermined hardwire but know predetermined hardwire but predetermined hardwire doesn't mean it's predetermined hardwire doesn't mean it's predetermined hardwire doesn't mean it's not modulated by learning or experience. not modulated by learning or experience. not modulated by learning or experience. It only means that you are born It only means that you are born It only means that you are born liking sweet and dislike in bitter. And liking sweet and dislike in bitter. And liking sweet and dislike in bitter. And we have many examples of plasticity. we have many examples of plasticity. we have many examples of plasticity. Coffee, it has an associated gain to the Coffee, it has an associated gain to the Coffee, it has an associated gain to the system. And that gain to the system, system. And that gain to the system, system. And that gain to the system, that positive veilance that emerges out that positive veilance that emerges out that positive veilance that emerges out of that negative signal is sufficient to of that negative signal is sufficient to of that negative signal is sufficient to create that positive association. And in create that positive association. And in create that positive association. And in the case of coffee, of course, is the case of coffee, of course, is the case of coffee, of course, is caffeine in activating a whole group of caffeine in activating a whole group of caffeine in activating a whole group of neurotransmitter systems that give you neurotransmitter systems that give you neurotransmitter systems that give you that that that high associated with that that that high associated with that that that high associated with coffee. So yes, this T system is coffee. So yes, this T system is coffee. So yes, this T system is changeable. It's malleable and is changeable. It's malleable and is changeable. It's malleable and is subjected to learning and experience. subjected to learning and experience. subjected to learning and experience. >> Can you imagine a sort of a system by >> Can you imagine a sort of a system by >> Can you imagine a sort of a system by which people could leverage that where which people could leverage that where which people could leverage that where does this this desensitizing happens does this this desensitizing happens does this this desensitizing happens that's the term that we use I think it that's the term that we use I think it that's the term that we use I think it happening at multiple stations happening at multiple stations happening at multiple stations it's happening at the receptor level it's happening at the receptor level it's happening at the receptor level i.e. the cells in your tongue that are i.e. the cells in your tongue that are i.e. the cells in your tongue that are sensing that sugar sensing that sugar sensing that sugar as you activate this receptor and it's as you activate this receptor and it's as you activate this receptor and it's triggering activity after activity after triggering activity after activity after triggering activity after activity after activity eventually you exhaust the activity eventually you exhaust the activity eventually you exhaust the receptor again I'm using terms which are receptor again I'm using terms which are receptor again I'm using terms which are extraordinarily loose the receptor gets extraordinarily loose the receptor gets extraordinarily loose the receptor gets to a point where it under goes a set of to a point where it under goes a set of to a point where it under goes a set of changes chemical changes changes chemical changes changes chemical changes where it now signals far less where it now signals far less where it now signals far less efficiently efficiently efficiently or it even gets removed from the surface or it even gets removed from the surface or it even gets removed from the surface of the cell and that is a huge side of of the cell and that is a huge side of of the cell and that is a huge side of this modulation. this modulation. this modulation. And then the next I believe is the And then the next I believe is the And then the next I believe is the integrated again loss of signaling that integrated again loss of signaling that integrated again loss of signaling that happens by continuous activation of the happens by continuous activation of the happens by continuous activation of the circuit at each of these different circuit at each of these different circuit at each of these different neural stations from the tongue to the neural stations from the tongue to the neural stations from the tongue to the ganglia from the ganglia to the first ganglia from the ganglia to the first ganglia from the ganglia to the first station in the brain stem a second station in the brain stem a second station in the brain stem a second station in the brain stem to the station in the brain stem to the station in the brain stem to the phalamus then to the cortex. So there phalamus then to the cortex. So there phalamus then to the cortex. So there are multiple steps that this signal is are multiple steps that this signal is are multiple steps that this signal is traveling. Now you might say why if this traveling. Now you might say why if this traveling. Now you might say why if this is a label line why do you need to have is a label line why do you need to have is a label line why do you need to have so many stations and that's because the so many stations and that's because the so many stations and that's because the taste system is so important to ensure taste system is so important to ensure taste system is so important to ensure that you get what you need to survive that you get what you need to survive that you get what you need to survive that it has to be subjected to that it has to be subjected to that it has to be subjected to modulation by the internal state and modulation by the internal state and modulation by the internal state and each of these nodes provides a new site each of these nodes provides a new site each of these nodes provides a new site to give it plasticity and modulation I'm to give it plasticity and modulation I'm to give it plasticity and modulation I'm going to give you one example of of of going to give you one example of of of going to give you one example of of of how the internal state changes the way how the internal state changes the way how the internal state changes the way the taste system works. works. Salt the taste system works. works. Salt the taste system works. works. Salt is very appetitive at low concentrations is very appetitive at low concentrations is very appetitive at low concentrations and that's because we need it. It's our and that's because we need it. It's our and that's because we need it. It's our electrolyte balance requires salt. Every electrolyte balance requires salt. Every electrolyte balance requires salt. Every one of their neurons uses salt as the one of their neurons uses salt as the one of their neurons uses salt as the most important of the ions, you know, most important of the ions, you know, most important of the ions, you know, with potassium to ensure that you can with potassium to ensure that you can with potassium to ensure that you can transfer these electrical signals within transfer these electrical signals within transfer these electrical signals within and between neurons. But at high and between neurons. But at high and between neurons. But at high concentrations, let's say ocean water is concentrations, let's say ocean water is concentrations, let's say ocean water is incredibly aversive. And we all know incredibly aversive. And we all know incredibly aversive. And we all know this because we gone to the ocean and this because we gone to the ocean and this because we gone to the ocean and then when you get it in your mouth, it's then when you get it in your mouth, it's then when you get it in your mouth, it's not that great. However, if I salt not that great. However, if I salt not that great. However, if I salt deprive you now, this incredibly high deprive you now, this incredibly high deprive you now, this incredibly high concentration of salt, one molar sodium concentration of salt, one molar sodium concentration of salt, one molar sodium chloride, becomes amazingly appetitive chloride, becomes amazingly appetitive chloride, becomes amazingly appetitive and attractive. and attractive. and attractive. What's going on in here? Your tongue is What's going on in here? Your tongue is What's going on in here? Your tongue is telling you this is horrible, but your telling you this is horrible, but your telling you this is horrible, but your brain is telling you you need it. And brain is telling you you need it. And brain is telling you you need it. And this is what we call the modulation of this is what we call the modulation of this is what we call the modulation of the taste system by the internal state. the taste system by the internal state. the taste system by the internal state. >> I'd love for you to talk about the >> I'd love for you to talk about the >> I'd love for you to talk about the aspects of gut brain signaling that aspects of gut brain signaling that aspects of gut brain signaling that drive our or change our perceptions and drive our or change our perceptions and drive our or change our perceptions and behaviors that are completely beneath behaviors that are completely beneath behaviors that are completely beneath our awareness. our awareness. our awareness. >> Yes. You know, the brain >> Yes. You know, the brain >> Yes. You know, the brain needs to monitor the state of every one needs to monitor the state of every one needs to monitor the state of every one of our organs. It has to do it. This is of our organs. It has to do it. This is of our organs. It has to do it. This is the only way that the brain can ensure the only way that the brain can ensure the only way that the brain can ensure that every one of those organs are that every one of those organs are that every one of those organs are working together in a way that we have working together in a way that we have working together in a way that we have healthy physiology. This is a two-way healthy physiology. This is a two-way healthy physiology. This is a two-way highway where the brain is not only highway where the brain is not only highway where the brain is not only monitoring but is now modulating back monitoring but is now modulating back monitoring but is now modulating back what the body needs to do. And that what the body needs to do. And that what the body needs to do. And that includes all the way from monitoring the includes all the way from monitoring the includes all the way from monitoring the frequency of heartbeats and the way that frequency of heartbeats and the way that frequency of heartbeats and the way that inspiration and aspirations in the inspiration and aspirations in the inspiration and aspirations in the breathing cycle operate to what happens breathing cycle operate to what happens breathing cycle operate to what happens when you ingest sugar and fat. Let me when you ingest sugar and fat. Let me when you ingest sugar and fat. Let me give you an example. So Pablo in his give you an example. So Pablo in his give you an example. So Pablo in his classical experiments in conditioning, classical experiments in conditioning, classical experiments in conditioning, you know, associative conditioning, he you know, associative conditioning, he you know, associative conditioning, he would take a bell, it will ring the bell would take a bell, it will ring the bell would take a bell, it will ring the bell every time he was going to feed the dog. every time he was going to feed the dog. every time he was going to feed the dog. Eventually the dog learn to associate Eventually the dog learn to associate Eventually the dog learn to associate the ringing of the bell with food the ringing of the bell with food the ringing of the bell with food coming. The dog now in the presence of coming. The dog now in the presence of coming. The dog now in the presence of the bell alone will start to salivate the bell alone will start to salivate the bell alone will start to salivate and we will call that you know and we will call that you know and we will call that you know neurologically speaking an anticipatory neurologically speaking an anticipatory neurologically speaking an anticipatory response. Neurons in the brain that form response. Neurons in the brain that form response. Neurons in the brain that form that association now represent food is that association now represent food is that association now represent food is coming and they're sending a signal to coming and they're sending a signal to coming and they're sending a signal to motor neurons to go into your salivary motor neurons to go into your salivary motor neurons to go into your salivary glands to squeeze them. So you release glands to squeeze them. So you release glands to squeeze them. So you release you know you know saliva because you you know you know saliva because you you know you know saliva because you know food is coming. But what's even know food is coming. But what's even know food is coming. But what's even more remarkable is that those animals more remarkable is that those animals more remarkable is that those animals are also releasing insulin in response are also releasing insulin in response are also releasing insulin in response to a bell. Somehow the brain created to a bell. Somehow the brain created to a bell. Somehow the brain created these associations and there are neurons these associations and there are neurons these associations and there are neurons in your brain now that no food is coming in your brain now that no food is coming in your brain now that no food is coming and send a signal somehow all the way and send a signal somehow all the way and send a signal somehow all the way down to your pancreas that now it says down to your pancreas that now it says down to your pancreas that now it says release insulin because sugar is coming release insulin because sugar is coming release insulin because sugar is coming down. Now the main highway that is down. Now the main highway that is down. Now the main highway that is communicating the state of the body with communicating the state of the body with communicating the state of the body with the brain is a specific bundle of nerves the brain is a specific bundle of nerves the brain is a specific bundle of nerves which emerge from the veagal ganglia the which emerge from the veagal ganglia the which emerge from the veagal ganglia the nos ganglia and so it's the vagus nerve nos ganglia and so it's the vagus nerve nos ganglia and so it's the vagus nerve that it's innervating the majority of that it's innervating the majority of that it's innervating the majority of the organs in your body it's monitoring the organs in your body it's monitoring the organs in your body it's monitoring their function sending a signal to the their function sending a signal to the their function sending a signal to the brain and now the brain going back down brain and now the brain going back down brain and now the brain going back down and saying this is going all right do and saying this is going all right do and saying this is going all right do this or this is not going to well do this or this is not going to well do this or this is not going to well do that that that >> and I should point out as you well know >> and I should point out as you well know >> and I should point out as you well know every organ spleen pancreas every organ spleen pancreas every organ spleen pancreas >> they all must they all must be monitored >> they all must they all must be monitored >> they all must they all must be monitored I have no doubt that diseases that we I have no doubt that diseases that we I have no doubt that diseases that we abnormally associated with metabolism abnormally associated with metabolism abnormally associated with metabolism physiology and even immunity are likely physiology and even immunity are likely physiology and even immunity are likely to emerge as diseases conditions states to emerge as diseases conditions states to emerge as diseases conditions states of the brain I don't think obesity is a of the brain I don't think obesity is a of the brain I don't think obesity is a disease of metabolism I believe obesity disease of metabolism I believe obesity disease of metabolism I believe obesity is a disease of brain circuits. I do as is a disease of brain circuits. I do as is a disease of brain circuits. I do as well. well. well. >> Yeah. And so this this view that we >> Yeah. And so this this view that we >> Yeah. And so this this view that we have, you know, been working on for the have, you know, been working on for the have, you know, been working on for the longest time because, you know, the longest time because, you know, the longest time because, you know, the molecules that we're dealing with are in molecules that we're dealing with are in molecules that we're dealing with are in the body, not in the head. You know, led the body, not in the head. You know, led the body, not in the head. You know, led us to, you know, to view, of course, us to, you know, to view, of course, us to, you know, to view, of course, these issues and problems as being one these issues and problems as being one these issues and problems as being one of metabolism, physiology, and so forth. of metabolism, physiology, and so forth. of metabolism, physiology, and so forth. They remain to be the carriers of the They remain to be the carriers of the They remain to be the carriers of the ultimate signal. But the brain ultimate signal. But the brain ultimate signal. But the brain ultimately appears to be the conductor ultimately appears to be the conductor ultimately appears to be the conductor of this orchestra of physiology and of this orchestra of physiology and of this orchestra of physiology and metabolism. Now let's go to the gut metabolism. Now let's go to the gut metabolism. Now let's go to the gut brain and sugar. The vagus nerve is made brain and sugar. The vagus nerve is made brain and sugar. The vagus nerve is made out of many thousands of fibers that out of many thousands of fibers that out of many thousands of fibers that make this gigantic bundle. And it's make this gigantic bundle. And it's make this gigantic bundle. And it's likely as we're speaking that each of likely as we're speaking that each of likely as we're speaking that each of these fibers, they carry meaning that's these fibers, they carry meaning that's these fibers, they carry meaning that's associated with their specific task. associated with their specific task. associated with their specific task. This group of fibers is telling the This group of fibers is telling the This group of fibers is telling the brain about the state of your heart. brain about the state of your heart. brain about the state of your heart. This group of fiber is telling the brain This group of fiber is telling the brain This group of fiber is telling the brain about the state of your gut. This is about the state of your gut. This is about the state of your gut. This is telling your brain about its nutritional telling your brain about its nutritional telling your brain about its nutritional state. They are again to make the same state. They are again to make the same state. They are again to make the same simple example the keys of this piano. simple example the keys of this piano. simple example the keys of this piano. Now the reason this is relevant because Now the reason this is relevant because Now the reason this is relevant because the magic of this gut brain axis the magic of this gut brain axis the magic of this gut brain axis is the fact that you have these is the fact that you have these is the fact that you have these thousands of fibers really doing thousands of fibers really doing thousands of fibers really doing different functions. Okay, let me tell different functions. Okay, let me tell different functions. Okay, let me tell you about the gut brain axis and our you about the gut brain axis and our you about the gut brain axis and our insatiable appetite for sugar. This is insatiable appetite for sugar. This is insatiable appetite for sugar. This is work of my own laboratory know that work of my own laboratory know that work of my own laboratory know that began long ago when we discovered the began long ago when we discovered the began long ago when we discovered the sweet receptors. You can now engineer sweet receptors. You can now engineer sweet receptors. You can now engineer mice that lack these receptors. So in mice that lack these receptors. So in mice that lack these receptors. So in essence, these animals will be unable to essence, these animals will be unable to essence, these animals will be unable to taste sweet. And if you give a normal taste sweet. And if you give a normal taste sweet. And if you give a normal mouse a bottle containing sweet and mouse a bottle containing sweet and mouse a bottle containing sweet and we're going to put either sugar or an we're going to put either sugar or an we're going to put either sugar or an artificial sweetener. All right, they artificial sweetener. All right, they artificial sweetener. All right, they both are sweet. They have slightly both are sweet. They have slightly both are sweet. They have slightly different tastes, different tastes, different tastes, but that's simply because artificial but that's simply because artificial but that's simply because artificial sweeteners have some off tastes. But as sweeteners have some off tastes. But as sweeteners have some off tastes. But as far as the sweet receptor is concerned, far as the sweet receptor is concerned, far as the sweet receptor is concerned, they both activate the same receptor, they both activate the same receptor, they both activate the same receptor, trigger the same signal. And if you give trigger the same signal. And if you give trigger the same signal. And if you give an animal option of a bottle containing an animal option of a bottle containing an animal option of a bottle containing sugar or a sweetener versus water, this sugar or a sweetener versus water, this sugar or a sweetener versus water, this animal will drink 10 to one from the animal will drink 10 to one from the animal will drink 10 to one from the bottle containing sweet. That's the bottle containing sweet. That's the bottle containing sweet. That's the taste system. it animal goes samples taste system. it animal goes samples taste system. it animal goes samples each one leaks a couple of leaks and each one leaks a couple of leaks and each one leaks a couple of leaks and then said uhuh that's the one I want then said uhuh that's the one I want then said uhuh that's the one I want because it's aitive and because I love because it's aitive and because I love because it's aitive and because I love it. Now we're going to take the mice and it. Now we're going to take the mice and it. Now we're going to take the mice and we're going to genetically engineer it we're going to genetically engineer it we're going to genetically engineer it to remove the sweet receptors. So these to remove the sweet receptors. So these to remove the sweet receptors. So these mice no longer have in their oral cavity mice no longer have in their oral cavity mice no longer have in their oral cavity any sensors that can detect sweetness, any sensors that can detect sweetness, any sensors that can detect sweetness, be that sugar molecule, be an artificial be that sugar molecule, be an artificial be that sugar molecule, be an artificial sweetener, be anything else that tastes sweetener, be anything else that tastes sweetener, be anything else that tastes sweet. And if you give this mice an sweet. And if you give this mice an sweet. And if you give this mice an option between sweet versus water, it option between sweet versus water, it option between sweet versus water, it will drink equally well from both will drink equally well from both will drink equally well from both because he cannot tell them apart because he cannot tell them apart because he cannot tell them apart because it doesn't have the receptors because it doesn't have the receptors because it doesn't have the receptors for sweet. So that sweet bottle tastes for sweet. So that sweet bottle tastes for sweet. So that sweet bottle tastes just like water. But if I keep the mouse just like water. But if I keep the mouse just like water. But if I keep the mouse in that cage for the next 48 hours, in that cage for the next 48 hours, in that cage for the next 48 hours, something extraordinary happens. When I something extraordinary happens. When I something extraordinary happens. When I come 48 hours later, that mouse is come 48 hours later, that mouse is come 48 hours later, that mouse is drinking almost exclusively drinking almost exclusively drinking almost exclusively from the sugar bottle. During those 48 from the sugar bottle. During those 48 from the sugar bottle. During those 48 hours, the mouse learned that there is hours, the mouse learned that there is hours, the mouse learned that there is something in that bottle that makes me something in that bottle that makes me something in that bottle that makes me feel good. And that is the bottle I want feel good. And that is the bottle I want feel good. And that is the bottle I want to consume. And that is the fundamental to consume. And that is the fundamental to consume. And that is the fundamental basis of our unquenchable desire and our basis of our unquenchable desire and our basis of our unquenchable desire and our craving for sugar and is mediated by the craving for sugar and is mediated by the craving for sugar and is mediated by the gutbrain access. So we reason if this is gutbrain access. So we reason if this is gutbrain access. So we reason if this is true and it's the gutb brain axis that's true and it's the gutb brain axis that's true and it's the gutb brain axis that's driving sugar preference then there driving sugar preference then there driving sugar preference then there should be a group of neurons in the should be a group of neurons in the should be a group of neurons in the brain that are responding to brain that are responding to brain that are responding to postingestive sugar postingestive sugar postingestive sugar and lo and behold we identify a group of and lo and behold we identify a group of and lo and behold we identify a group of neurons in the brain that does this and neurons in the brain that does this and neurons in the brain that does this and these neurons receive their input these neurons receive their input these neurons receive their input directly from the gut brain axis and so directly from the gut brain axis and so directly from the gut brain axis and so what's happening is that sugar is what's happening is that sugar is what's happening is that sugar is recognized ized normally by the tongue recognized ized normally by the tongue recognized ized normally by the tongue activates an appetitive response. Now activates an appetitive response. Now activates an appetitive response. Now you ingest it and now it activates a you ingest it and now it activates a you ingest it and now it activates a selective group of cells in your selective group of cells in your selective group of cells in your intestines intestines intestines that now send a signal to the brain via that now send a signal to the brain via that now send a signal to the brain via the veagal ganglia that says I got what the veagal ganglia that says I got what the veagal ganglia that says I got what I need. The tongue doesn't know that you I need. The tongue doesn't know that you I need. The tongue doesn't know that you got what you need. It only knows that got what you need. It only knows that got what you need. It only knows that you tasted it. This knows that it got to you tasted it. This knows that it got to you tasted it. This knows that it got to the point that it's going to be used, the point that it's going to be used, the point that it's going to be used, which is the gut. And now it sends the which is the gut. And now it sends the which is the gut. And now it sends the signal to now reinforce signal to now reinforce signal to now reinforce the consumption of this thing because the consumption of this thing because the consumption of this thing because this is the one that I needed. Sugar this is the one that I needed. Sugar this is the one that I needed. Sugar source of energy. So these are gut cells source of energy. So these are gut cells source of energy. So these are gut cells that recognize the sugar molecule. I that recognize the sugar molecule. I that recognize the sugar molecule. I see. see. see. >> Send a signal and that signal is >> Send a signal and that signal is >> Send a signal and that signal is received by the veagal neuron directly. received by the veagal neuron directly. received by the veagal neuron directly. Got it? And this sends a signal through Got it? And this sends a signal through Got it? And this sends a signal through the gutb brain axis to the cell bodies the gutb brain axis to the cell bodies the gutb brain axis to the cell bodies of these neurons in the veagal ganglia of these neurons in the veagal ganglia of these neurons in the veagal ganglia and from there to the brain stem to now and from there to the brain stem to now and from there to the brain stem to now trigger the preference for sugar. You trigger the preference for sugar. You trigger the preference for sugar. You see, you want the brain to know that you see, you want the brain to know that you see, you want the brain to know that you had successful had successful had successful ingestion and breakdown of whatever you ingestion and breakdown of whatever you ingestion and breakdown of whatever you consume into the building blocks of life consume into the building blocks of life consume into the building blocks of life and you know glucose, amino acids, fat and you know glucose, amino acids, fat and you know glucose, amino acids, fat and so you want to make sure that once and so you want to make sure that once and so you want to make sure that once they are in the form that intestines can they are in the form that intestines can they are in the form that intestines can now absorb them is where you get the now absorb them is where you get the now absorb them is where you get the signal back saying this what I want. signal back saying this what I want. signal back saying this what I want. Okay, now let me just take it one step Okay, now let me just take it one step Okay, now let me just take it one step further. This now sugar molecules further. This now sugar molecules further. This now sugar molecules activates this unique gut brain circuit activates this unique gut brain circuit activates this unique gut brain circuit that now drives the development of our that now drives the development of our that now drives the development of our preference for sugar. A key element of preference for sugar. A key element of preference for sugar. A key element of this circuit is that the sensors in the this circuit is that the sensors in the this circuit is that the sensors in the gut that recognize the sugar do not gut that recognize the sugar do not gut that recognize the sugar do not recognize artificial sweeteners. It's a recognize artificial sweeteners. It's a recognize artificial sweeteners. It's a completely different molecule that only completely different molecule that only completely different molecule that only recognizes the glucose molecule, not recognizes the glucose molecule, not recognizes the glucose molecule, not artificial sweeteners. This has a artificial sweeteners. This has a artificial sweeteners. This has a profound impact on the effect of profound impact on the effect of profound impact on the effect of ultimately artificial sweeteners in ultimately artificial sweeteners in ultimately artificial sweeteners in curving our appetite, curving our appetite, curving our appetite, our craving, our insatiable desire for our craving, our insatiable desire for our craving, our insatiable desire for sugar since they don't activate the gut sugar since they don't activate the gut sugar since they don't activate the gut brain access. They'll never satisfy the brain access. They'll never satisfy the brain access. They'll never satisfy the craving for sugar like sugar does. We craving for sugar like sugar does. We craving for sugar like sugar does. We have a mega problem with overconumption have a mega problem with overconumption have a mega problem with overconumption of sugar and fat. You know, we're facing of sugar and fat. You know, we're facing of sugar and fat. You know, we're facing a unique time in our evolution where a unique time in our evolution where a unique time in our evolution where diseases of malnutrition diseases of malnutrition diseases of malnutrition are due to over nutrition. Historically, are due to over nutrition. Historically, are due to over nutrition. Historically, diseases of malnutritions have always diseases of malnutritions have always diseases of malnutritions have always been linked to under nutrition. But I been linked to under nutrition. But I been linked to under nutrition. But I want to just go back to the notion of, want to just go back to the notion of, want to just go back to the notion of, you know, these brain centers that are you know, these brain centers that are you know, these brain centers that are ultimately the ones that are being ultimately the ones that are being ultimately the ones that are being activated by these essential nutrients. activated by these essential nutrients. activated by these essential nutrients. So sugar, fat and amino acids are So sugar, fat and amino acids are So sugar, fat and amino acids are building blocks building blocks building blocks of our diets and this is across all of our diets and this is across all of our diets and this is across all animal species. animal species. animal species. So it's not unreasonable then to assume So it's not unreasonable then to assume So it's not unreasonable then to assume that dedicated brain circuits would have that dedicated brain circuits would have that dedicated brain circuits would have evolved to ensure their recognition, evolved to ensure their recognition, evolved to ensure their recognition, their ingestion and the reinforcement their ingestion and the reinforcement their ingestion and the reinforcement that that is what I need. And indeed, that that is what I need. And indeed, that that is what I need. And indeed, you know, animals evolve these two you know, animals evolve these two you know, animals evolve these two systems. One is the taste system that systems. One is the taste system that systems. One is the taste system that allows you to recognize them and trigger allows you to recognize them and trigger allows you to recognize them and trigger this predetermined hardwire immediate this predetermined hardwire immediate this predetermined hardwire immediate responses. Yes. You know, oh my god, responses. Yes. You know, oh my god, responses. Yes. You know, oh my god, this is so delicious. It's fatty or this is so delicious. It's fatty or this is so delicious. It's fatty or umami recognizing amino acids. So that's umami recognizing amino acids. So that's umami recognizing amino acids. So that's the liking pathway. But in the wisdom of the liking pathway. But in the wisdom of the liking pathway. But in the wisdom of evolution, that's good, but doesn't evolution, that's good, but doesn't evolution, that's good, but doesn't quite do it. You want to make sure that quite do it. You want to make sure that quite do it. You want to make sure that these things get to the place where these things get to the place where these things get to the place where they're needed. They are needed in your they're needed. They are needed in your they're needed. They are needed in your intestines where they're going to be intestines where they're going to be intestines where they're going to be absorbed as the nutrients that will absorbed as the nutrients that will absorbed as the nutrients that will support life. And the brain wants to support life. And the brain wants to support life. And the brain wants to know this. Highly processed foods are know this. Highly processed foods are know this. Highly processed foods are hijacking, you know, co-opting these hijacking, you know, co-opting these hijacking, you know, co-opting these circuits in a way that they would have circuits in a way that they would have circuits in a way that they would have never happened in nature. And then we never happened in nature. And then we never happened in nature. And then we not only find these things appetitive not only find these things appetitive not only find these things appetitive and palatable but in addition we are and palatable but in addition we are and palatable but in addition we are continuously reinforcing you know the continuously reinforcing you know the continuously reinforcing you know the wanting in a way that oh my god this is wanting in a way that oh my god this is wanting in a way that oh my god this is so great what do I feel like eating let so great what do I feel like eating let so great what do I feel like eating let me have more of this. Well, this is why me have more of this. Well, this is why me have more of this. Well, this is why I think a lot of data are now starting I think a lot of data are now starting I think a lot of data are now starting to support the idea that while indeed to support the idea that while indeed to support the idea that while indeed the laws of thermodynamics apply, the laws of thermodynamics apply, the laws of thermodynamics apply, calories ingested versus calories burned calories ingested versus calories burned calories ingested versus calories burned is a very real thing, right? The is a very real thing, right? The is a very real thing, right? The appetite for certain foods and the the appetite for certain foods and the the appetite for certain foods and the the wanting and the liking are phenomena of wanting and the liking are phenomena of wanting and the liking are phenomena of the nervous system, brain and gut as the nervous system, brain and gut as the nervous system, brain and gut as you've beautifully described and that you've beautifully described and that you've beautifully described and that that changes over time depending on how that changes over time depending on how that changes over time depending on how we are receiving these nutrients. we are receiving these nutrients. we are receiving these nutrients. Absolutely. Understanding these circuits Absolutely. Understanding these circuits Absolutely. Understanding these circuits is giving us important insights and how is giving us important insights and how is giving us important insights and how ultimately hopefully we can improve ultimately hopefully we can improve ultimately hopefully we can improve human health and make a meaningful human health and make a meaningful human health and make a meaningful difference. difference. difference. Now, it's very easy to try to, you know, Now, it's very easy to try to, you know, Now, it's very easy to try to, you know, connect the dots A to B, B to C, C to D. connect the dots A to B, B to C, C to D. connect the dots A to B, B to C, C to D. And I think there's a lot more And I think there's a lot more And I think there's a lot more complexity to it. complexity to it. complexity to it. But I do think that the lessons that are But I do think that the lessons that are But I do think that the lessons that are emerging out of understanding how these emerging out of understanding how these emerging out of understanding how these circuits operate can ultimately inform circuits operate can ultimately inform circuits operate can ultimately inform how we deal with our diets in a way that how we deal with our diets in a way that how we deal with our diets in a way that we avoid what we're facing now, you we avoid what we're facing now, you we avoid what we're facing now, you know, as a society. I mean, it's nuts know, as a society. I mean, it's nuts know, as a society. I mean, it's nuts that the over nutrition happens to be that the over nutrition happens to be that the over nutrition happens to be such a prevalent problem. such a prevalent problem. such a prevalent problem. >> Yeah. And I also think the training of >> Yeah. And I also think the training of >> Yeah. And I also think the training of people who are thinking about metabolic people who are thinking about metabolic people who are thinking about metabolic science and metabolic disease is largely science and metabolic disease is largely science and metabolic disease is largely divorced from the training of the divorced from the training of the divorced from the training of the neuroscientist and vice versa. No one neuroscientist and vice versa. No one neuroscientist and vice versa. No one field is to blame. But I fully agree field is to blame. But I fully agree field is to blame. But I fully agree that the the brain is is the key over or that the the brain is is the key over or that the the brain is is the key over or the nervous system to be more accurate the nervous system to be more accurate the nervous system to be more accurate is the one of the key overlooked is the one of the key overlooked is the one of the key overlooked features features features >> is the arbiter ultimately is the arbiter >> is the arbiter ultimately is the arbiter >> is the arbiter ultimately is the arbiter of many of these pathways. On behalf of of many of these pathways. On behalf of of many of these pathways. On behalf of myself and certainly on behalf of all myself and certainly on behalf of all myself and certainly on behalf of all the listeners, I want to thank you first the listeners, I want to thank you first the listeners, I want to thank you first of all for the incredible work that of all for the incredible work that of all for the incredible work that you've been doing now for decades in you've been doing now for decades in you've been doing now for decades in vision, in taste and in this bigger vision, in taste and in this bigger vision, in taste and in this bigger issue of how we perceive and experience issue of how we perceive and experience issue of how we perceive and experience life. It's uh truly pioneering and life. It's uh truly pioneering and life. It's uh truly pioneering and incredible work. And I feel quite lucky incredible work. And I feel quite lucky incredible work. And I feel quite lucky to have been on the sidelines seeing to have been on the sidelines seeing to have been on the sidelines seeing this over the years and hearing the this over the years and hearing the this over the years and hearing the talks and reading the countless talks and reading the countless talks and reading the countless beautiful papers, but also for your time beautiful papers, but also for your time beautiful papers, but also for your time today to come down here and talk to us today to come down here and talk to us today to come down here and talk to us about what drives you and the about what drives you and the about what drives you and the discoveries you've made. Thank you ever discoveries you've made. Thank you ever discoveries you've made. Thank you ever so much. so much. so much. >> It was great fun. Thank you for having >> It was great fun. Thank you for having >> It was great fun. Thank you for having me. me. me. >> We'll do it again. >> We'll do it again. >> We'll do it again. >> I wish all