11. Introduction to Neuroscience II

Transcription for the video titled "11. Introduction to Neuroscience II".

1970-01-07T04:57:36.000Z

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Introduction

Intro (00:00)

Stanford University. I would like to get started please. So, my name is Patrick House. I am a neuroscience PhD student. I work with Robert and Robert's lab on the first year. And I study something that you guys will eventually hear about, but I don't want to ruin the punchline. But today we're going to talk about memory and plasticity. And so, two days ago on Wednesday, right, you guys all sat in here in this room, and you learned some of you for the first time, some of you for maybe the tenth time, the basics of neurobiology, of how a neuron works, how a neuron you have a presynaptic cell, you have a postsynaptic cell, and this kind of simplified version of the communication and information transfer. And something interesting happened between now and then, which is that now you sit in the same room, and something about you knows something about neuroscience now, right? You heard one of the TA's talk, you slept on it, and then you come back now and you have assimilated, integrated into your identity into what you know, new facts. And this lecture is about how you do that. And to kind of get at what memory is, we need to think about a lot of different ways in which it's interesting, and a lot of different kind of spectrums and severities about memory, right? So, why is it that some memories last our entire lives, whereas other memories we hear, and they're fleeting. They go away in a second. Why is it that someone who, someone sitting next to you in bed telling you a story, and as you go to sleep, you can't remember it. As you wake up, you can't remember your dreams. But if that exact same person, that exact same story was told to you, as they were sitting next to you in a car, and you get into a car accident, suddenly, that memory becomes salient. You may remember it for years if not your entire life, and you may actually associate either the story itself, the voice of the person, with that traumatic event, and you might get post-traumatic stress disorder. So, if the mechanism is the same between these two types of memory, between ones that are fleeting and forgetful, and ones that last your entire life, the question is, how does environment, how does context fit into shaping these types of memories? And so, in order to understand that, we have to kind of get at what are the mechanisms of memory, and how are these contextually motivated. So, I want to introduce to you first, Stephen Woldshire, who is an architect, if not in practice, at least in mind. He is an autistic savant, and he has been mute since age three. And he has this remarkable capacity, which I'm actually going to test you guys on slightly here, if you have any kind of inclination to sketch, or you happen to have some sketch paper with you. I want you to, this will take approximately 60 seconds to span across all of Rome, draw it from memory, in your 60 seconds, because Stephen Woldshire has this amazing capacity to take helicopter rides. He's done this over Tokyo, he's done this over New York, he's done this over Rome and over London. And in 20 minutes, he can then sit down and recreate every single building, every single column, every single window, in correct proportions, from the correct angle in which the helicopter ride was. And so, you may be thinking, okay, your 60 seconds are almost up. Can you guys do it? You may be thinking, okay, if any of you are artists out there, you may be thinking, this is unfair, why can't I do this? And as neuroscientists, our first thought is, okay, this is unfair, why can't I do this? But really, it can tell us something interesting about memory, right? So, you come at it with two questions. First question, before and after this helicopter ride, what is different in Stephen's brain? And second, on the steam of individual variation that we keep kind of harping on in class, why is it that he can do this and we can't do this? And these are two important questions that if we could answer those questions, we would know a lot about what memory is.


Concepts Of Synaptic Memory Storage And Neural Activities

Concept 1: Synaptic Memory Storage (04:33)

And so, it really makes sense to kind of go back to what it is that we know so far about neurons, the basics of one neuron and how it is activated, right? And so, we have a presynaptic cell and we have a postsynaptic cell. And in our simplified version, we can kind of know now, and what I'm going to tell you is that memory learning happens to the best of our knowledge in the synapse, in the place between the space between the pre- and the postsynaptic cell. But to understand why it is that we think that, we kind of need to go back about 100 years to when people, scientists, neuroscientists were investigating the brain, investigating memory. And they thought that the smallest unit of the brain that they knew was the neuron. So, because of our kind of tendency to explain what we don't know in terms of the smallest unit of thing that we do know, they thought, "Okay, this makes sense, right? A memory is a new neuron." And when you learn a new fact, when you learn the basics of neuroscience, you are growing new neurons, and each individual fact is associated with one new neuron. For instance, they may have thought that, "Okay, you guys learned on Wednesday that the axon and hillock is the site of the generation of the axon action potential." So, then that is a new fact, and then a new neuron would then be formed. And, okay, so that actually might not make, I just realized that that actually might not make sense because at the time that they thought that they didn't know what an axon and hillock is. So, maybe that formulation doesn't even make sense. But the idea is that a couple decades later, people discovered the synapse. They discovered that neurons were not just one interconnected thing, that there was space. There was a gap between them. And as soon as they discovered the synapse, that then became the smallest bit of information we knew about the brain. And then theories came out saying, "Okay, well, no, memory must be the formation of the brain." So, the dogma at the time was then that, okay, new fact, axon and hillock, what does this mean in the brain? You can see this in the brain. This takes the shape of a new synapse being formed. And what we think of now is that, well, this isn't exactly right because new synapses are not being formed all the time. And new neurons are not formed in the adult brain, which isn't entirely true, but we'll get back to that. But the idea is just that memory and storage of learning, what I'm going to tell you is that it's in the synapse, and that it involves modulation and change of the synapse. And why do we think that? Because we understand the molecules, and we understand at a molecular level what's happening in the synapse when it changes. And so that is thus now our smallest level of understanding of the brain. And so, of course, we think, oh, well, that's probably where memory is. So that's the dogma that we're going to start with. And we're going to start with this idea that memory is synaptic plasticity. Memory is when the space between a presynaptic and postsynaptic neuron changes in some way. And not only that, it changes in one direction. It gets stronger. It's strengthened. And so what this means is that if you have your presynaptic neuron and you fire it, and you get some amount of response, that over time if you give enough kind of presynaptic activation in a certain time window, that you will then get a heightened, strengthened response in your postsynaptic cell eventually. And that is the kind of mechanism, the overarching, broad mechanism of LCP.


Model of Hebbian Plasticity (08:15)

And so what we need to do, to understand memory, is to focus on the synapse. So what we get is our kind of classical picture, which is that you have your synapse and a neurotransmitter is coming out, and that neurotransmitter is excitatory. And in your postsynaptic cell, what you're getting is you're getting a small amount of activation. You're getting current that comes into that cell. You're getting ions, some sort of response for any individual piece of neurotransmitter. And you're getting a little bit more of a sense of the amount of activation. And you're getting a little piece of neurotransmitter. And so what this is, is a version, a simplified version of what is called "heavian plasticity." And so there's this guy, Hebb, which you have to know. There's a few kind of names you have to know in neuroscience, and he's one of them. And Hebb came up with this idea, the kind of only bumper sticker that neuroscientists ever have on their car, which is that neurons that fire together, wire together. What he's saying is that you have your standard picture of a very, very simplified version of a presynaptic cell that's releasing an excitatory neurotransmitter, and that when it does so, you get a response in your postsynaptic cell. And so the, if you will remember from kind of to one lecture ago, that that excitatory neurotransmitter is glutamine. And kind of, though, if you're going to spend any time and energy into remembering one neurotransmitter that might be relevant for the class, this is the one you want to remember. You don't have to remember it, right? So, mostly the idea is just that it's excitatory. And why is this important? It's because information is transferred in the brain through activation. And in order to transfer information, you need excitatory neurotransmitters. You need your neurons to be activated. But as we know, kind of from what I've told you so far, that repetition is what drives memory, I would suggest that you remember that glutamate is the excitatory and one and only neurotransmitter that you have to know that, say, there's a test question that says, "What is the one excitatory neurotransmitter in the brain that you have to know you would respond?" Glutamate, and then you would be right. And so you can imagine that for this type of simplified diagram, if we were to strengthen the synapse, if we were to get some sort of plasticity, some sort of change, potentiation, what you could think of a few ways of doing this, right? You could take the presynaptic neuron and change how much excitatory neurotransmitters are released. You could change how much glutamate is released. And presumably, if you release more of the little circles with positive charge in them, then you're going to get more activation in the post-synaptic cell. Another thing you could do is write basic kind of neurochemistry in this diagram is that each of those neurotransmitters is binding to a receptor on the post-synaptic cell. And so what you could do is take that individual receptor and you can make it respond more to a single individual unit quanta of neurotransmitter. Alternately, you could just increase the number of post-synaptic receptors on yourself. And all of these would be mechanisms by which you could take this very, very simple synapse and potentiate it such that you get the same release, you get the same neurotransmitter, and what you get is subtle, because LTP is often very subtle. You just notice that the response is slightly larger, right? Slightly larger response given the same amount of input, given the same amount of output of the presynaptic cell. And this is the entire idea of LTP, long-term potentiation. This idea that at your individual synapse you can potentiate it, you can change it, it is plastic. But there should be one large red flag here, right? Which is, okay, one of these kind of caveats is, well, your presynaptic neuron, how does it know whether or not LTP should be undergone? How does it know whether or not LTP has been induced? This requires a kind of communication between both the pre and the post-synaptic cell, right? That how would the presynaptic cell, which has already released its neurotransmitter, no? And what you get is this kind of heretical type of neurotransmitter that can actually, we call it a retrograde neurotransmitter, that can actually be sent back from the post-synaptic cell. And it's a gas, nitric oxide, is an example of one, it's what you get in your dentist. And it kind of goes back and diffuses back across the synapse and actually modulates how much neurotransmitter gets released from the presynaptic cell. So we have these mechanisms, right?


Hippocampus (13:00)

We have these mechanisms of LTP. And the question then is, where does this happen in the brain? And why is it that we believe that these are the places of LTP? And one of the kind of things you need to know, this is our first kind of dive into neuroanatomy, is you need to know the hippocampus, right? It was introduced to you last lecture, but if there's one neurotransmitter you need to know, it's glutamate, and if there's one kind of neuroanatomical structure you need to know at this point, it's the hippocampus. And so how, I'm kind of always jealous of these kind of these autistic savants that can memorize 10,000 digits of pie and, you know, take a helicopter ride and fully recreate the kind of cityscape of any city they see. And if you read interviews about how they do it, it's really interesting. So what they seem to do is not memorize such a sheet of a bunch of digits, a string of 10,000 digits of pie. They'll take a walk through their childhood town, and they'll say that they put one of the digits on each and every object, right? So your mailbox will be the first digit, and then your neighbor's door will be another, and their window will be a three, and then they are not kind of re-conceiving and reconstructing just a sheet of boring numbers. They're taking kind of spatial tours through their memory. And what this always kind of compels me to do is make these kind of visual mnemonics, right? So I'm going to give you a visual mnemonic for the one way you have to remember that the hippocampus is the site of memory and the site of LTP, in so far as this class is concerned, which is okay, hippo horse, right? We learned that last time, it looks kind of like a sea horse, but that doesn't really make sense. What if you think about this? What if you think about the hippodrome, right, back in Rome? Hippodrome was the circular arena where you had your little chariot races, right? Because of horse. Horse. And there's two different scenarios that I want you to imagine. The first is, do you guys remember Michael Jordan and Larry Bird? They had this commercial where they played horse, right? And what they were doing is they were playing, you know, you have to make a basketball shot and then the next one you have to remember. What that first person did exactly? And you have to recreate it, right? So what I like to imagine is Larry Bird and Michael Jordan playing a game of horse in the hippodrome, back in Rome. And then you can kind of get this idea of how memory is related to the hippocampus and this horse structure. And if that doesn't work for you, I have one more, which is actually my favorite, which is you can imagine the entire amphitheater, the entire hippodrome filled with people. And there's that one, there's that one emperor who named his horse as Senator. Do you guys know who that is? What's his name? I don't know his name. Caligula. Caligula. There you go. Okay. So imagine the entire hippodrome is filled with people and Caligula is there and he gets his senator horse in the middle of the field and the horse is sitting kind of cross-legged. And he's typing out your memoirs, okay, on a typewriter. And that is how you're going to remember that the hippocampus, the hippodrome, the horse is where memory is formed. Okay, so now you guys are all, you guys are all autistic spawns now. So really though, what we need to determine is, okay, why is it that we really think that the hippocampus is the site of LTP and memory formation? It turns out that there is actually adult neurogenesis and adult plasticity, right? So in the last 10 years we've discovered that the adult brain really does actually form new neurons. And for the last 100 years we kind of disregarded that and said those guys who initially believed that every new neuron is associated with every new fact, those guys were just totally wrong and ridiculous, what a ridiculous concept. And so perhaps eventually in the future we will have to incorporate this idea that there does seem to be some neurogenesis in the brain. But much like how we learned that there is non-genetic kind of inherited traits, right? Which we had learned from kind of the disreputable Lamarck way back in Lamarckian evolution that there is no for 100 years we thought no. And it turns out that there is no non-genetic inheritance of traits. But it turns out that, well, okay, we do seem to have some kind of non-genetic inheritance and so Lamarck isn't entirely wrong. And it turns out this is a kind of similar thing where the people of most disrepute are often just a little bit right. So probably people that used to think that adult neurogenesis has something to do with memory are probably a little bit right.


Memory II (17:52)

And we're going to stick with the canon, which is that LTP happens and that it happens not on the level of the neuron, not on the level of the synapse, but on the level of the plasticity of the synapse. And so why do we think it's the hippocampus? We kind of get at it from a few ways. The first way is that HM, this kind of well-dressed epileptic who had his hippocampus removed, right? And what happened was he had selective removal of just his hippocampus and he could no longer remember anything at all. You could not form new memories whatsoever. So with these types of conclusions, in addition to evidence that if you watch and record from neurons in the hippocampus, as you're giving someone a learning task, then you see LTP. If you pharmacologically block LTP, you see changes in the hippocampus. And so all these pieces of evidence are trying to get at the idea that the hippocampus is necessary for kind of memory and memory consolidation. But if you introspect a little bit, you can probably realize that, well, we undergo all kinds of forms of learning and memory, right? We have motor learning.


Storage and retrieval (18:57)

We learn how to shoot baskets. We learn how to throw darts. We understand kind of emotionally that events that are more emotionally salient are more memorable. And so how is it that these types of things are also encoded in our brain, also encoded in the same region, the one region, the hippocampus? And what that turns out to be is that, well, it's not just that one region. LTP is happening all over the brain that if you look in your emotional kind of regulation centers, if you look in your emotional cortices, you also see LTP. And this makes sense because these types of memories have to have different methods of storage and retrieval. And also that you can imagine this type of excitation, this type of synaptic plasticity can go wrong, right? In post-traumatic stress disorder, for instance, you get LTP and you get LTP that is severe. And you get severe LTP, potentiation of your synapses, in those emotion regulation centers that create a situation where the context leads to memories that shouldn't necessarily be brought up, that shouldn't necessarily be retrieved. And so we see this mechanism for types of behavior that we know, types of things like why certain memories, certain emotionally salient memories last for a long time and others don't. And we can also imagine that this is a physiological process and that it can go wrong occasionally, right? We all know that memories are degraded, sometimes intentionally so, sometimes unintentionally so, that there are certain things we want to remember, and despite any and all repetition about glutamate being the excitatory transmitter, we just don't remember them. And there are some that just kind of fade away into time, into the oceans, and what is happening is that there are mechanisms for intentional disruption of LTP. And you can think of a few, so hypoglycemic states, if you are really, really hungry, you get insulin kind of cascades that end up reducing LTP. And so, when you're starving, it's not a good time to try to remember things. It's a good time to try to go out and expend energy-finding food. As we'll learn later in lectures, there are some stress hormones, and these stress hormones actually give us a selective memory advantage in the short term, right? If you're in a car crash, you remember the slow-motion details of the entire event. And this has to do with these stress hormones, these fear hormones, coming out and saying, "Okay, well, we want to be able to remember this moment so we can learn from it next time if we survive."


Intentional disruption of LTP (21:50)

But if you do this chronically, if you do this for a long time window, throughout the lifetime of the organism, then you can actually get damaged LTP and damage to memory. So it's about time window. It's about the same mechanisms that can enhance memory, can also be deleterious eventually. And another kind of probably more familiar one, perhaps not to the introverts, but perhaps to the extroverts in the crowd, is that if this lecture were on Saturday morning, I could probably ask you guys what you did last night. And some of you would not be able to tell me with delicate accuracy what happened on Friday, and you might not be able to tell me the story that was read to you at bedtime, or even who read you the story of the story. And this is because ethanol, alcohol, directly disrupts LTP. And we see this and we see this in the hippocampus. And these are the types of things, behaviors that we know of. We know that emotionally salient memories last longer. We know that alcohol somewhat, there are differential effects of types of substances on memory. We know that it's hard to remember things right before we go to sleep. And so what's interesting is, can we get at a physiology that explains all of these things? And so I'm going to give you 60 more seconds. There's going to be a pop quiz at the end, by the way. You have 60 more seconds to do this. And what is interesting here is that when we get down to these kind of physiological mechanisms, and we have two ends of a spectrum, we have HM, and we have Stephen Woldt-Chiner, right? Someone who cannot form any memories whatsoever, and then someone who can do this in a 20 minute helicopter ride, recreate the entire landscape. And the question is, the theme of this class is often one of individual variation. How is it that one person can not be able to form any memories whatsoever? How is it that one person can have an autistic kind of photographic memory? And where do we fit? Where do people -- where does memory fit in a properly functioning way? And like most of the kind of spectrums that are introduced into this class, right, one of imprinted genes, tournament versus parabonding species, things like that, the answer turns out to be, we are somewhere in the middle between HM, no hippocampi, no formation of new memories, and Stephen Woldt-Chiner.


Areas of Investigation (24:25)

So one more thing kind of we need to discuss with the theme of this class is that often we'll give you a lecture, and then maybe in the next lecture, maybe in a five minutes later, we'll tell you it's all wrong. Or we'll say, no, you've been way too myopic. That's not how you should see these things. And what we need to do in order to understand somewhat about the context of memories is to take and expand your myopic view of this simplified version of a neuron, right? So far we've gone into what a single neuron functioning looks like, and we've gone into what a single neuron as it transmits a signal to another neuron looks like, how there's a gap in between the pre and the postsynaptic cell, and what that information transfer looks like, and how we can change that information transfer, how we can make it plastic. But there's a problem here, which is that if we're trying to learn anything about the brain, we have to understand that the brain is really complicated, and that there's 100 billion neurons, and that sometimes these individual neurons will connect to 10,000 other neurons. And sometimes each of those 10,000 neurons will have 10,000 neurons that connected to it. And so the question, the kind of first, I don't know, as a neuroscientist, when I look at that, the first thing I do is want to give up, right? And then I do. And then the second question, the second kind of thought is, okay, maybe it's time to expand the simplified version of the neuron that we have. It's not just one neuron talking to another neuron. It's not just a single synapse, but that it's the dynamics of many, many interacting neurons. And that kind of as these dynamics expand, as these dynamics get introduced into 10,000 neurons at the same time, 10,000 dendrites, dendritic arbors connecting to 10,000 other like axonal processes, then we see that things that didn't matter so much in the single individual neuron actually matter quite a bit when you're talking about 100 billion neurons, right? So one of the things to introduce here is the concept of noise into the individual signal transfer, into the individual information transfer. A neuron, as we presented it, was something that fires an action potential, transmits information. Every single action potential leads to neurotransmitter release, which leads to postsynaptic kind of response. But these are very delicate things, right? An individual neuron is constantly in flux with how much current is coming in and out. Ions are flowing around. It's not as simple as a static neuron that then gets activated and then passes on a message to another static neuron which then gets activated. What you get is often, a lot of times, you'll get random and spontaneous generation of signal, of action potentials, and sometimes of current in the postsynaptic cell. And one of the major tasks of the brain is figuring out, figuring out what is signal, what is appropriate and meaningful signal, versus what is this noise. If you can imagine on a single neural level, the noise might not have that much impact. But if you're talking about 100 billion neurons, you're going to get noise all over the place that will just kind of lead to this static of noise that you don't know what to make of the world anymore. You don't know what to make of the signal. You don't know what to make of individual neural signals. And so what we need to do is to start considering neurons in terms of how they interact in dynamics of groups.


Inhibition (28:17)

And one of the first ways and the most important way is to think about this is to understand that neurons are not just excitatory forces, that information, yes, is generated by kind of glutamate in the transfer of excitation, but that neurons have a capability to inhibit. And one of the important ways that they differentiate signal from noise, one of the important ways to learn what is noise and what is not, is to inhibit. And I'll explain how it is exactly that the inhibition works. But one of the first, no, that's pretty high. One of the first ones to understand is that a neuron can inhibit itself, which is not really, it seems like it could initially be some sort of masochism, but it's really not. It's just that the neuron is trying to sharpen the signal that it's sending, right? So a neuron is firing and firing over and over and over. And what it wants to say, what it wants to be able to do is accurately give a precise description of the signal, of the information. And what it can do is inhibit itself to say, I'm done. No more spontaneous noise, no more spontaneous little bits of current. I am done with my signal. And what this is, is it allows for temporal sharpening. It allows for the ability of a neuron to say, this was my signal, it was meaningful, I really meant it. You know, and inhibit the kinds of random noise and spontaneous things that could happen. Another aspect type of inhibition that's very important to separate noise from not noise is spatial inhibition. So what this is, is your individual neuron, not only can it send kind of processes and inhibit itself, it can actually send processes out and inhibit its neighbors. And how might this be kind of useful and important, is that it can say, essentially, okay, this signal is real. The signal is the signal that I want to send, the information that I want to transfer. And not only that, ignore my neighbors, it's really me. And what this allows you to do is get spatial sharpening. So what this allows you to do is say, in the kind of field of things that you're trying to perceive, a certain neuron will respond to a certain section of that field. And what this is saying is, I am activated and you kind of inhibit your neighbors so that you're more sure that your signal is true. And how can we relate this?


Pain Sensation (30:38)

How can we make sense of this? There's a very simple type of feedback network that should kind of elaborate this idea, which is pain and pain sensation. And so we all probably, at some point in our lives, presumably, have discovered and felt pain. And there's kind of two general qualities of pain. You can have really, really fast sharp pain and you can have this dull aching throbbing pain. And what people found when they investigate into your spinal cord and into kind of your sensory peripheral processes is how this pain is generated. And it's generated on two separate types of neurons. And one carries fast pain, one carries the sharp fast stuff, one carries the slow dull stuff. And what you find is that these are kind of intertwined in this delicate feedback loop such that the fast spiking first pain will generate kind of eventually the slow moving pain. It will fire the other neurons next to it, the neighbors, and say, okay, also start this kind of slow pain spike. But then the slow pain spike can come back and inhibit the first kind of sharp spike such that it stops. We're trying to get information about the world. And your body is trying to do what it can with that information. And if you get stung by something, you want really sharp pain to be like, hey, pay attention to that. Make sure it's not a scorpion that's still there. But you don't need the sharp pain forever. You want to be able to inhibit it and just say, okay, pay attention. But then, you know, just to make sure you don't walk on it anymore and get it infected, we're going to make it hurt a little bit. And so this is your body trying to make the most of this type of information. And what it's doing is using lateral inhibition in this complicated way, actually simple way, to allow for these two types of kind of transmissions of information. That was a very simple example. And I think there's a much more complex example when we go into the types of complex, kind of visual stimuli that vision gives us. And you can imagine that lateral inhibition, the same type of spatial sharpening of a signal, can come into play as we're trying to figure out and piece together the visual world. So what this is doing, what this kind of lateral inhibition allows for, is it allows for visual neurons to receive input and then to say, it is me, right? This is the signal that I want to send. Not only that, inhibit the neighbors. And what this leads to is this emergent property of these kind of retinal cells that allow for specific types of signal and allow for specific types of reciprocity. So in your eyes, your kind of neurons in the back of your eyes, if you just stand still, they only have a certain angle of light that they can get. And that idea is this idea of receptive fields. That they are responsible for that field. And they're responsible for saying, if there's a signal there, this is what it is and this is how it's relevant. And what this type of lateral inhibition allows you to do is it allows you to say, okay, I write your neuron gets a signal and it wants to say, okay, that's an edge, an edge detection, contrast detection. If you look around in the objects in the room, often you can define them by their edges. So we have this elaborated kind of neural mechanism involving inhibition and excitation that allows for this type of contrast enhancement. And what can we do with this kind of even more, right? So these guys, Hubel and Wiesel, decided that they were going to look, okay, another brief anecdote. So there's this commercial when I was young. And it was Michelin Tires, right? And if any of you guys ever become kind of marketing people, which there's enough of you that statistically someone will, I don't know why you don't make commercials that are scary, because this commercial frightened me. And I was like six. And I remember it to this day. So why not, if you want someone to remember your product, just make it. Like, take what you know from this and use it to manipulate people. That's what education is. And so I remember this commercial and I just remember it was for Michelin Tires. And their whole point was that no matter how fancy your car is, no matter how much you spend on your car, there's only four points of contact between you and the road, right? And it's on your tires. And I don't know why, but this blew my mind and it scared me. And it made me, okay, recognize that, yeah, you should get good tires. So Hubel and Wiesel, they took essentially the same logic, right? Which is that, okay, we have this complicated visual world and we know that we put it together somehow. But our only access to this information is through the retina, right? We have, okay, the light is the road. These are our two tires, right? We only have two tires to connect with the road. And so what they, their logic was that if we look at each individual neuron in the retina, we entrace it back. We should be able to see somehow how this visual world is constructed, how it is that we go from the road to the road.


Neurons at the back of your retina (36:04)

How it is that we go from the only signal, the only signal from the outside world we get to this complicated visual field. And what they, what they found was that if you look at the neurons in the back of a retina and then look at kind of where they get, where they synapse back in kind of your visual cortex, they found a one-to-one correspondence. That if you activate a certain neuron in your retina, you'll get a kind of spatiotopic, which means they're oriented in the same way and all the neurons are aligned in a similar way, field in the back of your visual cortex in V1. And so what that essentially means is that kind of your eyes are smushed to the back of your head, right? There's no information that necessarily gets enhanced or reduced between your retina and the back of your visual field. And they're like, okay, great. And so these guys, Hubel and Wiesel, they won the Nobel Prize. If you could win more than one, they probably would have won four by now. They're these Harvard neuroscientists back in the day, and they are pretty much the kind of who you need to know, right? You need to know hebb. You need to understand glutamate. You need to understand LTP and Hubel and Wiesel. If you're going to be a neuroscientist, be interested in the brain, they will come up. And if you're a neuroscientist, you have to invite them to your wedding and you have to do everything. I don't even know if they're-- they might even be dead. You have to say on to them or something. But what they decided to do was then, okay, now we're at V1. We're at the one level of visual cortex. What else can we do? Where does the scene get constructed that we see? And what they did was look one layer up. And they did the exact same thing. They fired an individual retina on their own. And they looked in the next layer up. And absolutely nothing happened. There was no activity anywhere. No matter what they did, they fired all of them. There was no activity. And they were like, oh, damn it. We're not going to get invited to any weddings. And what are we going to do? But what they discovered was that if you kind of activated enough retinal neurons and that they were in a certain spatial orientation, say a line, then you get activation in this other layer. Of your visual cortex. And what they discovered and what was on, I'm sure, the construction of all of their wedding invitations was that if you have certain neurons that are selective to certain orientations of lines like so. If you imagine these are four neurons, a single neuron will be responsive to a vertical line, a single neuron, another one, a different one will be responsive to a 45 degree angle, right? A horizontal line, 135 degrees. And so what you get, and you're starting to piece together, is this way of constructing the visual world that is layered. And that extracts out features. And that through those features, you get kind of individual neural activation. And you might imagine that if you go up even further, you would get some sort of more higher order types of activation, individual activation in your visual cortex. Something like, say, a neuron that only responds to an orange, or a neuron that only responds to a banana, or a neuron that, so this is one of the terms in the field, only responds to your grandmother, right? And they call it a grandmother neuron. And there's this kind of El Dorado type quest for grandmother neurons, right? Where can we find it? And the problem is nobody ever found it. And so then the question becomes, again, related to memory, related to even our understanding of these kind of networks of neurons, where are these memories stored? And so, to, well, this is slightly out of order. But basically, this is an example of, again, your lateral inhibition, right? So to understand how it is that these kind of signals are sharpened, right? This is a nice visual illusion. Do you guys see little dots of dark between each of those? That is an artifact, right? That is an artifact of your visual perception. That is an artifact of you constructing that. And why is that happening? Because at each of those individual corners, you're getting the most amount because of the four kind of axial bars of white of lateral inhibition. So in every single one of your brains right now, whenever you look at the individual corner, you're getting lateral inhibition. And so you can imagine that this type of thing is in a demonstration of lateral inhibition. Another type of thing. When I was talking about pain, right? So there's this fascinating thing where we all know this, where if something itches, that you have a mosquito bite, and you want to scratch the hell out of it because sometimes it feels really good, you notice also that you can scratch around it, right? You can make hard kind of painful stimuli in the immediate vicinity and just do it really, really hard enough and you get lessening of pain. And what that is is the same type of thing. It's lateral inhibition of the focal point of the mosquito bite. And so these things sound abstract, but these things really are real. And we can see them and we can feel them if we know where to look. So one last idea, right? We're trying to get at, okay, where are these memories stored?


Concepts and categories (41:26)

Where are these facts? Where is what you know now about neurobiology stored? And we kind of, it's helpful to introduce the idea of neural networks, right? There's 100 billion neurons in the brain. These are not communicating one to one. These are communicating with dozens, tens of thousands of other types of neurons. And if you simplify this down to just the basic idea of a neural network such that you have your kind of bottom first layer cells. And these first layer cells respond to, respectively, left to right, right? Monet, Cezanne, Degas. They just respond. For some reason, they have been tuned, they have undergone LTP. That is what they respond to. In this very one to one, Hubel and Wiesel kind of way. But what we notice is that there's this elaborate property you get when you start to combine neurons with many, many other types of neurons, which is that you get a network. And you get a network without one to one correspondence. So if you look at the top row and you get neurons A through E, A still responds in this one to one way with just Monet, right? E, again, you got just Degas. So those are not really informative in the way in which we want to understand the emergent property and what's important about neural networks. What we get out of neural networks is kind of emphasized when we focus on C, right? Neuron C doesn't know. If it gets activated, what can you tell? You don't know which kind of input it came from. You don't know whether it came from the first layer neuron one, first layer neuron two or three. You don't know whether or not it was a Monet, C, Cezanne or Degas. All you know is that it's one of those three. And what you get now is this idea that you can have concepts and you can have categories. And you can have a category of impressionism that doesn't necessarily give you information about individual types or names or which neuron it came from. But you have a network of neurons with different concepts in it. And amidst this network, you can now understand how it is that environment and context can impinge on the storage and retrieval effects, right? So the idea that emotionally salient memories are kind of longer lived in your brain, in your synapses, in your kind of plasticity than other ones. Well, how is that true if they're not contextually related, if the mechanism is the same everywhere? But what you begin to see is that if you combine context in this version of neural networks, you start to get the neural representation of context, the neural representation of environment. And this makes sense if you think about how we try to remember things, right? And you try to remember something and you know it's an impressionist painter, or you know it's within a category, but you're not quite there. You kind of take a tour of categorical ways of thinking and categorical learning and categorical objects in the world to try to get at that one fact, that one bit of information that you're trying to remember. So it's not that individual memories are stored in neurons, it's not that they're stored in the kind of the generation of synapses, it's not that they are stored in the entirely just the plasticity of single synapses, that it seems that we can get at and explain a lot of these types of memory by understanding that memory is kind of one aspect of a formation of these kind of neural networks, and that if we have 100 billion neurons, we can imagine elaborate and complex ways of designing these things. So here we go, one more time. Many very different things happen when we remember, right? Everything down from the synaptic plasticity all the way up to this impressionism categorical way of thinking and remembering about things. And what is, again, interesting here is that you can imagine what we've learned about polymorphisms, right? Genetic individuality and variation. That certain people can have different stress responses. The person next to you can have a different response to stress than the other person. One person will be more afraid of public speaking than the other person. One person will respond a certain way based on prenatal, postnatal environment, all these different things, all these different variations, these polymorphisms, that lead to individual and varied behavior. And now we can understand that kind of a polymorphism in how much presynaptic glutamate gets released. Remember, glutamate excitatory. A polymorphism in how strongly your postsynaptic receptor responds. A polymorphism in the ways in which your kind of neural networks are constructed. These types of individual things, which each are their own variable in this kind of brain, in your brain's construct of memory, can lead to different and individual ways in which we remember. Some people are just better at remembering than others. And what we're trying to get at is from the spectrum of HM, I can't remember anything, to Stephen Wilchier, who can remember this, and where the genetics and the environment kind of impact our individual memory.


Autonomic nervous system (46:55)

And I think that's it. So we'll take a five minute break. And I'm going to talk to you guys about the autonomic nervous system. So basically, autonomic sounds like automatic. This is anything that's going to happen automatically in your body. Not quite the hippocampus, horse, like hip and drums and drums. So we have automatic autonomic. So basically, like your heart feeding, digesting, goosebumps, orgasm, things that you don't have the control over, that is good stuff, right? This is going to be your autonomic nervous system. So first the nervous system, remember, is split up into the central and the peripheral. So our central nervous system is our brain and our spinal cord, and our peripheral nervous system is everything else on the periphery. And then within that the peripheral nervous system can be split up into the somatic nervous system and the autonomic. So we're going over the autonomic, remember that. But just to tell you about the somatic, that's basically the voluntary nervous system. So like, if you want to pick up a pen off the ground, you know, your brain says, "Okay, I want to pick up a pen, send the message to my muscle. "I want to pick up the pen." It's also your sensory info. So when you touch something or smell something, information from the periphery going to your central nervous system. And the autonomic nervous system, what we're going to talk about today, can be split up into the parasympathetic and sympathetic nervous systems. We'll go over all those in detail, but for right now, one last comparison of the voluntary and autonomic. So the voluntary nervous system, remember voluntary, moves muscles.


Autonomic System And Its Functions

Voluntary Vs Autonomic (48:44)

Autonomic, it's involuntary, moving organs, your heart, your digestive system, your lungs. The voluntary nervous system is actually myelinated. So what that means is there's a myelin sheath covering the axon, as you can see there. And the actual potential actually can speed up and go down the axon faster. And the autonomic nervous system is actually unmyelinated. These are just fun facts. So it goes a little bit slower. Okay, good stuff. Autonomic nervous system. So we have sympathetic and parasympathetic. And like sympathetic is that nervous system where you hear a fight or flight. So anything exciting, arousal, alertness, emergency, like if you have a hippo chasing after you or something, definitely sympathetic nervous system. If you like somebody and are like talking to them first time, sympathetic nervous system activation, you're excited. Parasympathetic is more of the calm vegetative function. So after you have a huge meal or when you want to take a nap, anything like that, grow for a pair, just like total relaxation state. And as you can see, they kind of sound like they have opposing functions because they do. And they tend to work in opposition. So it's kind of like putting your foot on the gas and the brake at the same time. You can't really do that because they're opposing. When the parasympathetic system is on, your sympathetic nervous system is usually off and vice versa.


Sympathetic (50:09)

So they work together to like keep our body going automatically. Sympathetic nervous system. So remember, this is like that huge animal. Whatever your favorite one is chasing after you. What do you do? Right? Well, your heart speeds up. It's going to beat faster. You're going to breathe more. You're going to vasoconstrict. So what that means is you're sending the blood. You're basically constricting your blood vessels and sending blood and work your lungs into your muscles so you can run away. You're going to inhibit digestion. Like when you're running away from a hippo, like you don't care about digesting the sandwich you just had. You're going to sweat. Your muscles will tense. There's anything you would think of when you're just like totally freaked out. Right? And the parasympathetic nervous system. So yeah, I really like these pictures. I like them, the dog, and I got super excited. And then I found him, and I wanted to name him, but I haven't thought of it yet. But basically they're resting and digesting, right? They're just taking it easy, like growth, repair. Basically anything you would do when you're not stressed, you have time to do now. Your immune system can function well. You can spend time digesting and urinating. Okay. Sympathetic nervous system. So we're going to look into the neurotransmitters involved in both the symptoms now. So like how on our neurons, like what's being communicated? And I know that Pat told you glutamate's the best, but I'm going to like fight that and tell you that norepinephrine is one of the good ones too. Basically you release norepinephrine in the target organs when you're dealing with the sympathetic nervous system. So the hip will coming out you right. What you do is you're going to release norepinephrine and E onto the target organs. And like you can see the organs on the left or the right, it affects all of those. So it's going to your heart, it's going to your lungs, it's going to your kidney, your bladder, and it's telling it when it receives norepinephrine, those organs know.


Adrenaline (Epi) (52:10)

Okay, my sympathetic nervous system is activated. I'm going to like fight or fight. I'm going to run away right now. Or I'm going to start like my heart's going to be faster. And the one exception is the sympathetic nervous system actually releases epinephrine in the adrenal. And this is just a cool exception. Epinephrine, right? Remember it's one step away from norepinephrine in the biosynthetic pathway. So you can make epinephrine from norepinephrine so they're not really that different. And also it's epinephrine is also called adrenaline, right? Adrenal adrenaline. See the resemblance. And this is just another diagram again showing you norepinephrine released on the target organs. So you think of sympathetic, you think of norepinephrine. And you can see how it will go and like accelerate the heartbeat, stuff like that. And just more in detail, if you've taken Bio-core, and I don't know about home Bio-core, but definitely Bio-core, you know that it's not that simple. You don't need to worry about this, but there's actually an intermediate step where the spinal cord projections actually first go to this ganglion, which then goes to the target organ and releases any there. But don't worry about that. Just know norepinephrine is sympathetic. Okay, parasympathetic nervous system. So we have another cool neurotransmitter besides glenoid and NE, which is exeocolatine or ACH. And the parasympathetic, you see it goes to all the same organs, but now when it releases ACH, those organs know parasympathetic. Resting digest. Like I have time to finish my meal and do everything that I can do when I'm on a relax. And again, there is an intermediate step where you release exeocolatine first in the target organ and then a second neuron goes. It releases exeocolatine again. There's no ACH parasympathetic. And if you want more details about it too, this slide is totally extra detailed, but you can see the projections from the spinal cord actually leave from different places and the parasympathetic and the sympathetic nervous system. And you can just see at the end, exeocolatine and norepinephrine being released. So this is a really important slide. That slide put stars on it. Even suppose he saw my PowerPoint, he's like, spend a lot of time on that slide. So I'm going to. So we're going to look at exactly what happens when your parasympathetic or sympathetic nervous systems are activated and compare them to in different organs. So the easiest one to start with is your cardiovascular system, so your heart. You're running away. You're scared. Or you're meeting someone new for the first time that you really like and your sympathetic nervous system turns on. Your heart is going to be faster. Remember that? So your heart actually has a mild genetic rhythm, which means it actually has a muscle that is controlling its beating. But what the brain does in the sympathetic and parasympathetic nervous system does is it can change how fast the heart beats. So your heart's beating faster. Your blood pressure will increase when your sympathetic nervous system is on. You're going to vasoconstrict, remember, send the blood to your muscles so you can run away and all that good stuff. And parasympathetic, right? Opposite. Slow or heartbeat like vasodilation of the vessels. Blood's now going to the GI tract for digestion and everything like that. Another front example is the GI tract itself. So your gut, your stomach, your small intestine. So basically, parasympathetic activity, when you're resting, you have time to digest. So what you do is you stimulate the secretion of the acids and enzymes needed for digestion. You move your small intestine with a contraction called peristalsis. And basically, you can go to the bathroom and everything that you do while you're relaxing. And then, so, sorry. Okay. So in the heart and the GI tract, you can pretty much see that they're like working in opposition.


Parasympathetic (56:15)

So like when the heart beats up with sympathetic, it slows down with parasympathetic. GI, the opposite case, right? Parasympathetic turns it on, speeds up digestion. Parasympathetic turns it off. I'm sorry. This is the important slide. Okay. So one place where they actually do work together instead of actually composing each other is in the male reproductive system. And they work together for you to erect and ejaculate. So what happens is in order to have an erection, right?


Male Reproduction & Blood Pressure (56:51)

You have to be stress free. You can't be worrying about your test. So which one do you think is in charge of erection? Parasympathetic or sympathetic? Perfect. So parasympathetic activation, you get an erection. Okay? Now let's say you have an erection and now you're like with somebody maybe. I don't know what you're doing. But like whatever's happening, like, sorry. Okay. So your heart, like all of a sudden you feel your heart beating faster. You start sweating a little bit, right? Your sympathetic nervous system is turning on a little bit now. So now we have parasympathetic. We still have our erection, but like we also have some sympathetic activity. And then more and more sympathetic activity. And all of a sudden, sympathetic activity completely takes over. And what happens? You ejaculate, right? So parasympathetic erection, sympathetic ejaculation. And it's actually a cool fact about erectile dysfunction is that about 60% of the cases are due to stress and not actually organic basis in your body, right? So if you're stressed out all of the time, your parasympathetic activity won't turn on. So you can't have an erection. And also we can explain premature ejaculation if you want to to your friends tonight. You can just be like, well, let's think about it. So I have an erection, but I'm going to ejaculate too soon. So parasympathetic transition to sympathetic transition, or the parasympathetic transition to sympathetic, happens too quickly.


How to Make White Blood Cells (58:23)

You premature ejaculation, okay? And then like health, right? So immune system. When your parasympathetic system is on, you can take care of your immune system, right? You have the time to make the white blood cells, but when you're chasing away from like a predator or like an elephant, you really don't care about making you white blood cells. And this could also explain why it's easier to get sick when you're stressed out. Your sympathetic is like too much caring about your stressful situation than taking care of your immune system. Okay? I don't know. Oh, my computer goes on sleep. I think that's it. Okay. So again, we see there's a balance between the two branches. So sympathetic, you're chasing away from a snake. When that's on, parasympathetic is off and vice versa. And there's actually a really cute video that I found. And you have to click it twice. Okay. So yeah. So the sympathetic nervous system, right? This like video will tell you everything that I just told you. It increases heart rate, makes your people's dialect so you can see further, run away from the predator. You don't have time to digest. You don't care about nasal secretions right now. You're not going to produce a lie about who cares about eating. Like, or inhibits the liver, kidneys, and gallbladder. And stimulates sweating, right? We're going to sweat when we're running away. It's getting scared. Causes pyloractants so your hair is done when you're nervous. It makes the lungs dilate and you can breathe faster. It increases muscle strength that way so you can run away. And it's important for Oregon. Sorry. Okay. Parasympathetic opposite. So it makes your heart rate go down. People's going to contract. You're going to digest. You're going to like the nasal secretions now. You're going to stimulate the liver, the bladder, and the kidneys. You can restrict your lungs, right? You're going to pay more attention to your digestion. It's important for sexual violence. Remember erections. Okay? And you can play again later. Okay. So an important point to make is when we think about sympathetic nervous system, we're thinking about arousal, emergency fight or flight. But that doesn't mean it always goes to the Oregon and excites it. So like, yeah, in the heart. When norapurnefin goes from the sympathetic nervous system to the heart, it does excite the heart and make it beat faster. But when it goes to the GI tract and inhibits the GI tract activity. So it's not always excitatory. It's not always inhibitory. It depends on the Oregon. Same with parasympathetic. We think of it as being the slower moving one. But in the GI tract, it does excite it. In the heart, it inhibits. So what does that mean? That means we need two different receptors on our organs that respond to norapurnefin or excitocoline. So on the heart, for instance, for norapurnefin, you'll have an excitatory norapurnefin receptor because it will get excited and will make the heart beat faster.


Autonomic Responses And Plasticity

Beta Blockers! (01:01:46)

But in the GI tract, you'll have an inhibitory norapurnefin receptor that will respond to the sympathetic nervous system and slow it down. And then for the parasympathetic, you would have an excitatory ACH receptor on your GI tract to speed it up to digest more food. And you'll have an inhibitory ACH receptor on the heart to slow it down. So to see, you can't always have the same receptor on the same organ. And it wouldn't respond right. And this is just showing you again. So the heart there, you have your inhibitory ACH receptor, which tells your heart to slow down. Excitatory norapurnefin, heart speeds up. And then in the GI tract, if your ACH is coming your way, it will attach to the excitatory receptor and it will digest. And you have the inhibitory norapurnefin receptor there too. So sympathetic activity is being simulated norapurnefin will land there and it will slow down digest in. And so, like if you've taken BioCore, if you want to know more, there's actually names for all these forms of receptors that I put there just in case you're interested. But on the heart, I think the coolest form is the beta blocker. The coolest factor about it is the beta blocker. So the form of the receptor on the heart that responds to the sympathetic nervous system is actually called a beta receptor. And what beta blockers do, right? They block the receptor, the beta receptor. So this is why beta blockers are used for like slowing down heart rate, reducing hypertension, basically blocking the effects of the sympathetic nervous system. And Pat actually just told me, it's great, that the one drug that's like banned from the Olympics are actually beta blockers. Because if you think about it, like a huge advantage would be like to be less stressed so that if they're blocking the receptor on your heart that like responds to stress and like the sympathetic nervous system, you can see how it could allow you to relax more. So it's a fun fact. Okay, so now we're going to talk about the regulation of the autonomic nervous system. So what's happening in the brain that's resulting in norepinephrine or exo-choline being released. And the center of regulation is now the hypothalamus. So yeah, we just talked about the hippocampus. So this is a different area of the brain, the hypothalamus. It's going to be very important on Monday as well when Tom and Will talk about the endocrine system because the hypothalamus directly affects the pituitary gland, which is center of their endocrine system. So basically the hypothalamus here contains the cell bodies or just like one synapse away from all the cell bodies that project onto the target organs, right, from the spinal cord to the target organs. So basically the hypothalamus will tell the spinal cord what to project onto the organ, okay. So an example of this would be like in your heart. And this is actually called the baroreflex. And this is just an example of how your hypothalamus is going to help your body maintain status quo. So like make sure that your blood pressure is never too high, your heart's beating at a normal speed. So like let's say your hemorrhaging because I don't know, like a hyena just attacked you. So anyways, you're hemorrhaging and you're losing a lot of blood. So your blood pressure is going to go way down and you have these like receptors in your blood vessels that are called baroreceptors and they'll say, okay, blood pressure is way too low. What do I do? They're going to send that info to the hypothalamus. Remember the hypothalamus center of regulation and the hypothalamus will be in charge of sending that information along to the spinal cord, which will then project onto the heart and tell it to beat faster. Sympathetic nervous system will be activated. Beat faster, increase my blood pressure so that you'll like make up for the loss of blood that you just had, okay.


Sweating in a Test (01:05:40)

And the opposite would happen if your blood pressure was getting too high or something, maybe the info will be sent to your brain and then you can decrease blood pressure through the parasympathetic nervous system. Okay, so reptiles, everybody kind of has that hypothalamus control of the, yeah. Oh, because remember like one's on or off? Yeah. So like, actually, like which one's normally on? Yeah. I think, do you guys know? Anybody know? Yeah. Okay. So, what about like mammals, right? Mammals have emotions and we have an emotional regulation like air in our brain that's called the limbic system. And we're going to learn a whole lecture just about the limbic system in general, but basically has everything to do with emotions, behaviors, memories, all mammalian type things. And like, so now we see this realm where not just, you know, losing all your blood can activate or stimulate the nervous system and like cause a parasympathetic or sympathetic response, but now just like seeing someone you hate like can cause the sympathetic response is very similar to like losing a lot of blood. And this is pretty amazing like will debase for instance if they see their enemies, they'll go, the info will be sent from just the smell of their enemies to the limbic system, project onto the hypothalamus, spinal cord, and then you can see them. Spinal cord to the sympathetic nervous system be like, I don't like you response. The sympathetic nervous system wanting to like either fight or flight, right? And then in the realm of primates, we also have our cortex. And what the cortex does is it makes thoughts and memories really important. So now instead of just having, you know, losing a lot of blood, like changing how our body functions and now just like not even having a sense, like we don't need to have a sense, we can just think about a thought and that can go ahead and change the way that every organ in our body functions, which is pretty amazing. So like when you're thinking about a test for instance, you're going to activate your cortex and this will activate your limbic system, then your hypothalamus. So that's known actually as the trying system of the brain is you have the cortex and primates mostly, then you have the limbic system, mostly million mammals, and then you have the hypothalamus, right? So it's going to go to each one of these like layers of the brain and just thinking about a test and causes sympathetic response where you start sweating, getting nervous, stressed out. And it's pretty amazing that just like if you lost a lot of blood in a reptile, that's kind of, we can simulate the same response, just thinking about something or thinking about something on the other side of the world dying. It's just amazing what like primates can do. And an interesting example of this, and I think we're having a lecture on depression, so I don't want to give it all away yet, but if you think about it, like the symptoms of depression, loss of pleasure, pain pathways on, don't want to have sex, aren't in the mood to eat, you're exhausted all the time. A lot of these symptoms are the same symptoms you would see if your sympathetic nervous system was overly activated, and we can see how a cortex having bad thoughts can go and activate that system in the same way, links to depression.


3. Autonomic Plasticity (01:09:06)

Okay. And the last thing I wanted to talk about in terms of the autonomic nervous system was the plasticity of it. So we just learned like the plasticity, right, in neurons, in the synapses, so that this one can change over time, and the autonomic nervous system can actually change over time in terms of how receptive or when it turns on and off. And a molecular example of this is if like you're a very stressful person and you're stressing all the time, well then you need a lot of norepinephrine, right? What do you do if you're stressing all the time? You increase the synthesis of the enzyme called tyrosine hydroxyylase, I believe. Yeah, it's up there. And basically this is the rate-limiting step in making norepinephrine, so if you increase more of the enzyme, you increase more of the norepinephrine, you can sustain the stress response. Another example, a solid-year example, is that we have projections from the sympathetic nervous system to the skin, eyes, nose, like everything that's going on up there. And let's say we see something scary. We can make those receptors more sensitive to that scary thing, so we can say, "Hey, it actually smells that enemy. You can make it seem scarier, and the sympathetic nervous system can turn on faster, so sensitization." There's also the opposite end of the spectrum where like you habituate to the things that are going on outside, so like, scary stimuli, like if you see a spider in your room the first time, you're probably going to freak out when you're younger. And lots of sympathetic activity, running away, fight or flight, you decide to fly because I don't like spiders. But basically after a while, the second time you see a spider, you're just like, "Okay, this is still scary. Maybe I'll run away." The third time, maybe you'll decide whatever, I'm just going to leave it there at this point, and you're habituated to it. So you've made the thresholds of your sensory receptors. They don't care as much. They don't respond as much. And the last example, when we're talking about cognitive thought and the cortex and what that can do to change your autonomic nervous system, is that it's an example of biofeedback and blood pressure. So basically, if you have high blood pressure, you can go into the doctor's office and you have two options, right? You can take medicine or you can try biofeedback. And what they do is they tell you to think of a pleasant thought. So like, think of your favorite vacation or think of your favorite person or just think of the beach in general. And what you'll see is that your blood pressure will actually decrease with a certain thought. And then the doctor will tell you to think about that thought again. Your blood pressure will decrease. And thinking more and more about that thought, helping your blood pressure decrease, what you do is you potentially, remember, you make stronger the connection where a cortical thought can go ahead and activate more sympathetic tone, have less sympathetic tone. So we're like potentiating that pathway, which a thought can cause our blood pressure to decrease, which is pretty cool.


Concluding Points

4. Take Home Points (01:12:05)

Okay. So take home points if you want to just like know what to remember from this. Know the broad difference between autonomic, automatic, right? And the voluntary nervous system, what we talked about at the beginning. Understand the neurotransmitters involved in each and why you need two types of receptors, right? The inhibitory and excitatory. Know one or two examples of what the parasympathetic, that's what PNFs by the way means. And sympathetic nervous system due to an organ. So remember the heart, the digestive tract, the male reproductive system. And then know a broad overview of how the brain regulates the autonomic nervous system. So hypothalamus, cortex, right? And we have the limbic system. Okay? And on Monday we're going over endocrinology. And so have a good one.


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