MITOCW MIT9_14S09_lec05-mp3 MALE SPEAKER: The following content is provided under a Creative Commons license. Your support will help MIT OpenCourseWare continue to offer high quality, educational resources for free. To make a donation or view additional materials from hundreds of MIT courses, visit MIT OpenCourseWare at ocw.mit.edu. GERALD SCHNEIDER: As you were taking the quiz, I remembered since several of you bring computers, you might want the file that has these. Now I posted the journal file. So if you don't have a tablet PC, that means you'll have to download Journal Reader from Microsoft if you want to read the file. Then they'll look just like this. I do it that way because some of you-- if have a tablet PC, this is the one you have to make anyway. And this is what I always use in my lectures. And then I make the PDF file afterwards from this. So I posted it on the website under class five. This is just a couple of terms at the beginning. Notochord and spinal cord. Spinal cord is c-o-r-d. Notochord is for some reason n-o-t-o-c-h-o-r-d. It gets confusing for some people, but I just want to show you the way I use them and what I want you to use. We're going to talk about the ancestor of the brain of the ancestor of mammals. And we'll sketch the brain. We'll sketch some basic pathways today. But I'm going to start with this phrase, ontogeny recapitulates phylogeny. What does that mean? The idea is that in development the brain and body go through a series of stages that resemble what the brain and body went through in evolution. And it's based on the simple fact that embryos at the very early stages look the same as embryos of other-- All the mammals look very similar in the early stages. In fact, at early stages, all the vertebrates look similar. And that was pointed out first by von Baer, 1828. And then von Haeckel had a very simple way of summarizing that that I'll also show you. This is from the von Baer illustrations. Although this particular picture comes from a later book. Along the right side here, you have a human. Very early stages here, and then a 1
little later here, and much later here. And then you add these other species as listed at the bottom. And just notice that at the very earliest stages, they all look very similar, from fish right up through human. But a little later in embryology, with the development of the embryo, they start to diverge. The human continues to be a little hard to distinguish even from the rabbit at that stage. A few mammals are already diverging a little more, like here the hog. But for fish and salamander, they look totally different now. And that by the time you get to late stages, the human is looking still like monkeys and apes. But it is not looking so similar anymore to the rabbit, and the calf, and the hog. It's certainly very different from chicks and tortoises and, of course, the amphibians and fish. This is the way Ernst Haeckel showed it. He said that, yes the gastrulas look very different in different animals. But all the members of the chordate phylum go through what he called the phylotypic state, where they all had very similar appearance. And then with development they diverge more and more. It was an oversimplified view, but it certainly conveyed the basic idea that ontogeny recapitulates phylogeny. Never look at that as a law. It is a resemblance. And it's true for some aspects brain development too. So those kinds of pictures with the whole embryos certainly lead you to expect similarities in the CNS of all the vertebrates. And yes we can definitely find them. And of course the brains of the mammals look even more similar. All the major components of the brain that we'll talk about today, you find in humans and you find in any other mammal, and in fact, all of the vertebrates today. Then of course when we start adding the cortex to the picture of the early brain, you begin to see how a mammalian brain is differentiated. So we're going to use a schematic outline of connections in pre-mammalian brains. This is based on a brain diagram that Nauta used to using his lectures. He didn't put this one in his book. But it was very popular. We used to laugh at the diagrams because we said they just looked like the cartoon called "The Schmoo." There was a cartoonist in Chicago named Al Capp who had 2
this comic strip running on "The Schmoo." And the whole body of the Schmoo looked like the brain that Nauta drew. And of course you remember, we're talking about very long periods in evolution. We talked about that earlier here. So this Schmoo brain, the first one that we'll show today, Nauta used to say you could think of it as a generalized amphibian brain based on the work of C. Judson Herrick and others. But if we look at it from the perspective of evolution, it could represent a cynodont. These were the animals, the mammal-like reptiles that mammals came from. And there's very nice pictures of that in Allman's book here, if any of you've been able to get this. Unfortunately, publishers let it go out of print even though it's not that old. He shows us a cynodont skeleton, for example, that was discovered in a sleeping posture curled up just the way mammals conserve energy when they sleep. Although, they don't actually know whether the cynodonts had mammary glands or hair the way the mammals do. Its relevance is that you could think of it as the old chassis that is the structure upon which all the mammalian brain has been built in evolution. You still have that brain, even in our brain. So there's no connections and no parts here that aren't still present in our brains. And we'll talk about some of the major evolutionary transitions as we go along. This is what they think cynodonts looked like based on reconstructions from skeletons by paleontologists. They existed from the late Permian age through the Triassic and Jurassic periods into the Cretaceous period. And I've given a website where you can find these things. And I mentioned Allman's chapter five there. And if you look on the web, you can find not only reference to cynodonts, but you'll see a list of, for example, the early mammals. These are all extinct mammals. But you can find information on all these. And you notice, I've underlined in red there, three of them that were already present in the Triassic period, so really early. At the time of the dinosaurs, they were little mammals. And their big problem then was how to avoid being eaten by the lizard, which were the dominant animal on earth at that time. And by the way, from that 3
paleontology, you can actually reconstruct the shape of the brain because we have the skulls. And from the shape of the skull, you can make an endocast. And you can pretty much see the shape of the brain and the major components. So it's not that we know nothing about the brain. The brain itself leaves no fossil remains. So we'll go through this Schmoo brain, point out the basic subdivisions, the basic types of neurons. And we'll review definitions, many of which we had before. And you'll get a few new ones. And then later we'll go through the main, what we'll call, channels of conduction, from input to output. I'll give an overview of core brain structures. And then later we'll add the neocortex to it. So let's go through some subdivisions first and point out where these different types of neurons are located. First of all, let me just enlarge this. You can get this, of course, on the web and review it. As I point out here, I want you to study the names and the subdivisions and learn to separate them. And notice here that the way it's drawn inside the spinal cord is of course unrealistically fat there. And the brain is, of course in reality, relatively a lot larger. I should have brought-- Maybe I have it here. I'll show you some-- I didn't actually bring the endocast results from cynodonts, but you would see relative sizes of these brain components. So here's the spinal cord. I have the Latin there also. There's the hindbrain. And the rostral part of the hindbrain is where the cerebellum develops. And then the midbrain with these little hills. Now that's dorsal surface, the colliculi. And then everything rostral to that line which separates midbrain from forebrain. This is all forebrain. First the diencephelon caudally. And then the telencephelon, or endbrain, rostrally. Now for the diencephalon, our tween brain, I'm just showing thalamus and hypothalamus. And attached to the hypothalamus, there's the pituitary, a neural part and a granular part. Now there's actually two further components of the diencephalon that we'll bring those in later. There's one way up here called the epithalamus and one in between the thalamus and hypothalamus we call the 4
subthalamus. But these two are the major ones. When you're reading your anatomy, these are the ones you're usually going to encounter, the thalamus or the inner chamber and the hypothalamus that is below the thalamus. So then everything rostral to that line is endbrain. And the sub-cortical components, so the corpus striatum and various sub-cortical components of what we call the limbic system, things closely connected with hypothalamus. And then we have the cortical structures, the surface structures. And the cortical structures are a lot of olfactory cortex. You could include the olfactory bulbs as cortex. And then a lot of this endbrain here is related to the mammalian limbic cortex. But even in that cynodont up brain, we're quite certain from its similarity to reptilian brains and amphibian brains, there's also what we call a dorsal cortex. And that was the predecessor of the neo-cortex. Yes? AUDIENCE: Professor, in between the two red lines, that's the forebrain? And then the other side, the endbrain? GERALD SCHNEIDER: Here are the lines. Everything between the two dark red lines there is tween brain. So everything rostral to this is forebrain. So there is forebrain. All forebrain. And I shouldn't do it like that because we'll confuse the-- The tween brain and endbrain are all forebrain. That's all forebrain. So forebrain, and then midbrain, hindbrain, spinal cord. Those are the major divisions. So now we'll spend a little time looking at trying to make sense of this bowl of spaghetti here. This is a little more complicated picture that Striedter uses, but basically it just adds a few details to my little Schmoo brain. Little more complex, but if you study that, you'll find most of the same things. He's named a few additional things. And I've explained the meaning of some of those Latin terms here in the picture. Now a more realistic view without such distortions we can get and still keep it very simple. If we take an embryo, the early embryonic mammalian brain. And what I've done here is to picture it from the dorsal side. I've left off the cerebellum, which 5
develops, remember, right in this region. I just leave it off because it would cover things here. And then these outpouchings at the front end, the cerebral hemispheres. They grew out of the side. But very early they come together over the top. And then they fold back. So I've not shown that. I push them out to the side. And the horizontal striations, they are covered, very thin wall of the ventricle there, where the neural tube is very thin, one cell thick. And that is true for the growth of hindbrain there. It's the roof plate that's stretched out for the hindbrain. And it's true there in the tween brain. It worked for the tween brain. And parts of the endbrain there that you can't see when the brain is-- And these two hemispheres come together. So this is all the neural tube. And it's what happened to the neural tube as it begins to develop. Look at the spinal cord here. I'm showing the sections. You can see, it's a tube with their lateral walls that have become thickened. The wall of the neural tube at the top and bottom, the roof plate and floor plate are still one cell thick. Here in the hindbrain, the roof plate is stretched out. Otherwise, it's very similar to the spinal cord, but it's enlarged. So that section was taken right here. Then here I show the midbrain, where again it looks a little distorted from the spinal cord. But you can still make out the walls of the neural tube that become much thicker eventually. Only later in development do they get thicker at the top as well. So the top there, above the ventricle we call the roof, the tectum. And then the tween brain right in there. Again a little more like spinal cord. It's called the walls of the neural tube. Right and left sides, they become thick. We still have that very thin roof plate, which you see here. And at the very bottom where the floor plate was before, now we can see this development of the pituitary region. And then finally the hemispheres, where the ventricle-- There's now two of them, one in each hemisphere. 6
All right. Let's look at some of the neurons now. First primary sensory neurons. And then we'll define some other neuron types there too. Remember, we looked at primary sensory neurons briefly before. And I showed you Cajal's picture here, where he shows primary sensory neurons in a series of animals. But these are sensory neurons all carrying information from somatic sensation from the body surface. These are located in the surface epithelium. And so do you find anything like that in this picture? Yes, right here. There's a primary sensory neuron in the nasal epithelium. That's the only sensory system where we have that. And there's the axon of the primary sensory neuron that comes through the skull and contacts secondary sensory neurons in the olfactory bulb. We'll color the secondary sensory neurons green. What about other primary sensory neurons? Well, what about these bipolar types? Do we have any of those? Yes we do, in this nerve. There's a bipolar cell. This is the eighth cranial nerve. Those neurons are bipolar in shape. And they come into the hindbrain and contact secondary sensory neurons in the cochlear nuclei and vestibular nuclei. And finally, this pseudo-unipolar shape like the dorsal root ganglion cells. And the 32 dorsal root ganglion on either side of the spinal cord. So this is an axon of a spinal nerve. And they're contacting the secondary sensory cells there in the dorsal horn of the spinal cord. So what else can we see? Well we can see motor neurons. The motor neurons here are blackened in. And notice they go from here down to here. Above the midbrain, you do not find motor neurons leaving the central nervous system that contact muscle cells. The rostralmost ones are in the midbrain. You also have them in the hindbrain in the ventral horn and the spinal cord. Notice also that there's one type here that rather than the axon contacting a muscle, it contacts a ganglion cell outside the CNS. So there's another motor neuron right there that's in a ganglion. That's in an autonomic nervous system ganglion. It could be parasympathetic or 7
sympathetic. So we talk about the pre-ganglionic motor neuron, which is in the CNS, and then the ganglionic motor neuron, which is in a cochlear cell outside the CNS. And that's the way glands and smooth muscle visceral organs are innervated. And by the way, these axons here are axons of the first cranial nerve, the olfactory. I only show those two cranial nerves. We usually talk about 12 cranial nerves. And there's actually many more if we include all the different vertebrates. But usually 12 are named for the mammals. And we'll be talking about those. And you will memorize them. It'll become so easy. When you talk about each of them many times, pretty soon you just remember them. I don't remember ever actually memorizing them, I just eventually knew them. You know them by number. You know them by name. You know them by function. You know whether they contain inputs, outputs. And you know about where they are. That will grown on you with time. So I think we talked about all of that, except what's left? The other neurons. Well, they're all interneurons. They're part of the great intermediate network. And we have to try to make sense of that network. So let's try to do a little more of that. Usually do that in two steps. I did it all in the one diagram. Now let's talk about channels of conduction. So now we can begin to make sense of some of those connections. Let's talk about a local reflex channel and maybe some not so local channels. Left my wireless card in. And then we'll talk about the lemniscal channel. The word lemniscus means a ribbon, a ribbon of axons in this case. So let's specify here. A local reflex channel. Let's follow the axon from this nerve. And we'll start there in the skin and follow it into the brain. And note that the axon of this cell contacts an interneuron in the cord, which then contacts a motor neuron, and goes out and stimulates muscles. All the conduction there that I've just drawn could be within one segment of the spinal cord. So that is the most local of local reflex channels. 8
So we talk about the segmental reflex. A reflex, remember, is just a stimulus here triggers a response, usually without much regard to the motivational state of the animal. And other reflexes involve more than one segment of the cord. So then we talk about an intersegmental reflex. We can even talk about supersegmental reflexes if it involves neurons, if it goes up to the brain stem here. But what do we mean by local? What do we mean by segment? So let's talk about the segment in the CNS. And in the periphery, we'll define the term dermatome. Dermatome, a section of the skin. First, just look at the gross anatomy here. This is the section I showed you once before, the human brain. There's still dura, the canvas-like covering, the outer covering. The outer meningeal layer has been left on. And it's covering the brain and the spinal cord there. But then you see the spinal nerves that aren't part of the CNS at all. Now if we saw the vertebrae, which were cut away here, they would be like this, with the spinal on the back there. This would be our vertebrae. And then here's another one. Now those vertebrae, those bones enclose the spinal cord. And they interdigitate with each other. And what separates them? The intervertebral disks. You've heard about what happens when you get a slipped disk. What kind of slipped disk is this? It can press on one of these nerves. Note that the nerves are coming out in between the vertebrae. So if the disk slips, it could be pressing on one of those nerves. Each vertebrae covers one segment roughly speaking. And each nerve primarily innervates one dermatome, one section of the skin. So note how this guy here is divided up. We start with C2 innervates the back of the head, innervates the upper part of the neck. And then we can go down to C8. Now C8 is innervating part of the arms. And then we get to thoracic. There's T1 and then T2 to T12. There's 12 thoracic segments of the spinal cord. And then we go to the lumbar level. This is the lumbar part of the back. Lumbar region in front. And then we have sacral region. Some people would name the 9
coccygeal region 2 for the very caudal end. And it helps to understand it if you put a human in this quadruped position. If we made this guy stand and lose his balance, we could make these lines even straighter, these vertical lines that are separating the dermatome. And here you have the cervical segments, thoracic segments, lumbar segments, and sacral segments. You see why those lines in the legs and arms there look a little complex. But they don't look so complex when you put their limbs in the right positions here. And note that the roots here separate into these different-- they each come in a spinal nerve. But the spinal nerves can join together and form the peripheral nerves. And this is what they're showing here. So the peripheral nerves don't have the same organization as the spinal nerves. But when you get out to periphery, the order that those nerves use to innervate the body surface fits the order of the roots. And notice that there's a little overlap. The skin innervated by thoracic level two overlaps with the skin innervated by T1 and T3. And usually they overlap with the one on either side. So that's what a dermatome is. They were mapped by two different methods. One is hypersensitive regions from irritation of a single spinal root, for example from a herniated disk. That region can become sensitive to inflammation or irritation of the nerve. And you can map it out. And you can also get it by the method of remaining sensibility. If you get severance of adjacent spinal nerves or dorsal roots, you can see what's left, if there's an isolated one. Sometimes we use this term myotome to mean the muscles innervated by a single ventral root. It's not as commonly used. But there is a matching myotome for each dermatome. So a local reflex that is really segmental might involve one dermatome and the corresponding myotome. And the only reflexes I know that are likely to be that local are the muscle to muscle reflexes, the stretch reflexes. Now let's talk about these ribbons of fibers, the lemniscal channels. Lemniscus meaning ribbon. And the first lemniscal channels carry some of the sensory 10
information up to the brain. And I've lumped two of them together, because these are the earliest ones. The spinal reticular, which is mainly uncrossed. It's actually bilateral, but it's mostly uncrossed. And the spinal thalam, which is mostly crossed. And then finally, the spinal cerebellar channels, which we're not going to get to today. Spinal reticular is really a rostral extension of what we call the propriospinal fibers. That is the fibers that connect one part of the cord with the other. They never leave the cord. It's a lot of inter-connections within the spinal cord. There's a lot of behavior that just depends on those inter-connections. The main organization of walking in all animals depends on spinal organization. The brain is just needed to modulate it. But we walk because of our spinal connections. And these are bilateral, but mostly ipsilateral. The spinal reticular fibers reach the core of the reticular formation of the brain stem. A few of them even make it all the way to the thalamus. We can guess about the functions. It's an understudy pathway in mammals, because the other pathways have become bigger. We study where the light is. So we think it does functions and autonomic control, like heart rate, blood pressure, breathing rate. We know that from where it projects and various autonomic and defensive behavioral responses to pain. Temperature regulation, which is represented in spinal level right on up to the core brain. And it also plays role in sexual behavior. And some of the modern neuroanatomy texts that you get in medical school never even mention it. But the Carpenter book that Nauta liked certainly had a nice picture. You can see how complex these anatomy books can get because they like to use human brain sections, when you don't have any background in neuroanatomy, are almost impossible to figure out. But I hope by the time this class ends, they won't be so difficult for you to figure out. But here it shows the spinal reticular pathway in humans and the axons that do make it all the way to rostral to the midbrain. And it shows a couple of descending 11
pathways that we won't talk about now. Now that's all the time we have. So we'll take up these primitive living vertebrates and talk about these pathways-- 12