Hello, everyone. Welcome to medical neuroscience and welcome to our first tutorial on the Functional Micronanatomy of Neurons. As we think together, I have three learning objectives for us to consider. First, I want you to be able to describe in very basic terms the classes of cells found in the central nervous system. I want you to be able to focus on one particular class that we'll spend much of our time in unit one of this course considering, the neurons, and I want you to think about the functional microanatomy of neurons. Now, I'll spend this tutorial explaining what I mean by that, but essentially I want you to be able to differentiate between the different parts of a typical neuron in terms of their structure and their function. And then lastly, I want you to be able to describe how that microanatomical structure of a typical neuron is compounded many thousands of times into the structure of neural tissue. And when we think of neural tissue, we're basically talking about grey matter, and white matter. Okay. Well let's begin by looking deep into the brain. And to do that, I'm going to show you a slide that I prepared some years ago. Through the motor cortex of human brain. So we're looking at just a few hundred square microns of tissue that has been stained with a particular dye called Thionine to reveal the presence of what we called Nissl substance, which is basically the. the rough endoplasmic reticulum or the machinery that's making proteins within cells. So it's just a great way to look at the cells that are present in tissue and to appreciate something about the composition of this tissue. So we're looking here and we can see a variety of different types of cells. And, indeed, the brain is a very complicated place even from a histological perspective. So, there are a variety of types of cells here and I think we can roughly categorize them into three types. There are neurons, which are the primary processors of neural signals. And as I mentioned we're going to spend a lot of time together thinking about neurons. There are neuroglial cells, which are the subject of the next tutorial. And neuroglial cells, or just glia for short, perform a rich variety of functions. And just to summarize those functions I would say they support the electrical And the chemical function of neurons. And then of course, the brain being a high, highly vascular structure requiring a constant supply of blood and that blood comes nutrients, such as glucose, oxygen and the ability to eliminate waste substances like carbon dioxide. So with that rich supply of blood that we find throughout the central nervous system we'll find vascular endothelium cells in brain tissue as well. So let's focus now on a neuron, and I'll make a few general remarks first and then we'll get on with our survey of the microanatomy of a typical neuron. So neurons are the fundamental unit of function in the central nervous system. This is a very important point and this is the reason why we'll spend so much of our time and energy in unit one thinking about how neurons actually, actually function. Now, for those of you who have a bit more background in the field of neuroscience or are more in tune with contemporary thinking in the field of neuroscience you'll realize that some might challenge this dogma that's been with us since the debate of Ramon y Cajal and Camillo Golgi more than a century ago. So with the more modern discussions for the aficionados acknowledged, I would continue to assert that the fundamental unit of function in the central nervous system is indeed the neuron. Now, neurons possess all the metabolic machinery that are common to other somatic cells so there's a region of the neuron that contains the nucleus and many of the organelles that are necessary. For cellular life so in that respect neurons are very much like other somatic cells. But in several important respect neurons are quite distinct. Neurons come in a rich diversity of form. And we call that form morphology, so when one sees diversity of morphology you should be thinking that there might also be diversity of function or physiology. And indeed, that's the case as form and function and structure are intimately connected within the central nervous system, even at the level of individual brain cells. Neurons have unique bioelectrical properties that distinguish them from most, but not all other somatic cells. For example, the machinery that's necessary to generate electrical signals in muscle cells is quite similar to what we see in most nerve cells. And finally, there are specializations for intercellular communication that are pretty unique to the nervous system. And for many neurons, most neurons in the mature central nervous system. This involves the secretion of special chemical molecules called neurotransmitters. Now again neurons have not evolved this capacity, independently of other kinds of cells in the body, there are other secretory cells that are well known in other kinds of tissues. But the challenge of inter-cellular communication demands some pretty interesting and some pretty unique specializations that we'll come to shortly. All right. Now lets survey the different parts that make up a typical neuron such as the one illustrated here. And this will give us the chance to think about what I consider to be the functional microanatomy of neurons. And let's begin with the cell body. So neurons have cell body which as I mentioned contains all the essential organelles importantly including the nucleus that are common to other somatic cells. And for most neurons, the cell body is actually quite rich in organelles because of the incredible synthetic capacities that are required for neurons to maintain their morphology as well as to support their function. So we find an abundance of endoplasmic reticulum, both smooth and rough, for example, for the synthesis of lipid molecules and proteins, respectively. We find an abundance of mitochondria for the generated the enormous energy supply that's necessary to keep neurons functions within their homeostatic states. So, for a variety of reasons, the cell body is a very important component of the neuron. Now from that cell body grow out numerous different sorts of protoplasmic extensions, and I would like to draw your attention to one set of extensions which are typically short, about 100 microns in length, and they emanate in all different directions from the cell body. These are called dendrites. Now, dendrites are very important for the microanatomy of a neuron, because what they do is that they extend the surface area that allows the cell to receive inputs from other neurons. So wherever we see dendrites we think of this as an input zone because dendrites are the means by which cells receive synaptic contacts from other neurons. Now some synaptic contacts are made directly into cell bodies, but for the most part we find them on dendrites. Now, dendrites also have some very peculiar, very fine microstructural features and these called spines. So, if I can illustrate just the length of a dendrite for you. I'll show you what I mean. Imagine that's a dendrite, and if we were to look at very high power, we might see under a microscope that there are these tiny, mushroom-shaped protrusions. Out the side of that dendrite, these are called spines. Sometimes they're not quite so mushroom like in they're shape, they're more of a filament that extends some short distance away. And sometimes there seems to be a little stalks and a protrusion at the tip of that stalk. So collectively, these yet increase the surface area of even a single dendrite, and provide a place for synaptic contact from other neurons. So wherever we see a spine, we can be quite confident that there is a synapse in one state of formation or another from the axons that are surrounding that dendrite. Now, not all dendrites grow out spines. Some dendrites are smooth. And where we see cells that grow out smooth dendrites we know that these cells tend to be those that have an inhibitory effect on the cells that they make synaptic connections to. So the presence or absence of spines on dendrites is one means by which we can classify neurons. And we know that, that classification based on the morphology of the dendrite. Gives us some insight into the functional properties of those cells. The morphology of dendrites is one way that we can differentiate various classes of neurons. Even among those that do in fact grow out spines. One of the very interesting types of cells that we find in the cerebral cortex is call the pyramidal neuron, and it's called that because the cell body is shaped something like a little pyramid. And from that cell body grow out a series of dendrites, and from the apex of the pyramid is one rather thick, stout dendrite that we call the apical dendrite because it grows out from the apex towards the surface of the brain. At the base of the pyramid are a variety of other dendrites called basal dendrites. And this special apical dendrite might have some unique ...properties, with respect to its role in receiving signals from other neurons, and those might be somewhat distinguished from those in the basal dendritic tree. So the distribution of dendrites is, again, another important way that we have of classifying different kinds of neurons. Some neurons are multipolar. And these neurons give rise to dendrites that seem to just emanate in all different directions without necessarily growing out a single apical dendrite. So again, another example of how dendritic morphology can give us some insight in to the structure and physiology of different cells in the brain. All right, so let's continue our survey. Now growing out from the cell body is a very particular protoplasmic extension, that has unique properties that allow it to generate electrical signals. And this process is call the axon. Now, whats illustrated here is a fairly simple picture of what a typical axon might look like. Its a single process often that grows out from the cell body and can grow for some distance some axons are short. Being less than 100 microns and others are very long. In fact, some are incredibly long. Consider for example a cell that might have it's cell body in the motor cortex right about here inside your head and that cell has to grow an axon all the way down through the brain, through the brainstem and into the spinal cord. Perhaps some length in the spinal cord, maybe even to the lumbar or sacral segments of the spinal cord. So that could be maybe a half a meter or more, depending upon your height. Or consider the motor neuron in the spinal cord itself that's going to send an axon out in a spinal nerve to innervate a muscle. If you're a very tall person that axon might be close to a meter in length, really an amazing dimension considering the fact that the cell body itself is probably close to about 50 microns in diameter. So that gives you the sense of how much bio synthetic capacity must be built in to these neurons as well as some insight as to their Need for, the energy. And the raw materials that's necessary to grow out and maintain the function of that axon. Now, on the function of that axon.This axon has the ability to generate an electrical signal. It's a special signal that we call an action potential. And we'll talk more about that in a later tutorial. That action potential is regenerated along the length of the axon and in that way it propagates from cell body towards the terminal ending of that axon. So for that reason, we think of the tissue that contains the axons as a conducting zone and allows for the flow of information from cell body towards axon terminal. Now, at the end of these axons, that's where we find our synaptic terminals, or synapses. And these are specialized contacts that allow one neuron to transfer a signal to another. They come basically in two varieties. We'll say more about these in a later tutorial. There are electrical synapses that have specialized junctions that allow charged molecules to pass directly from one neuron to another, and with it is conveyed the electrical signal. Other kinds of synapses are chemical, which is that there is a space or a gap or a cleft from one neuron to the next. In that cleft is breached by a chemical that synthesize and released by one neuron, diffuses across that space, and then interacts with receptors on another. So, there's a chemical message that mediates the electrical signal from one neuron to another. We'll have a lot to say about synapses, how they work what are the important regulatory mechanisms that control synaptic activity as we progress through unit one. So much more on synapses as we go. Now, what I'd like for us to do is to consider how this brief survey of the micro anatomy of a single neuron could be compounded many tens of thousands times in the structure of neural tissue. Now, imagine tens of thousands of neurons arraigned in parallel, very much like the one we're looking at here. And what I want you to appreciate about this parallel organization is that where we find the cell bodies and the dendrites, that is, the input zone of one neuron, we'll find the input zone of many thousands of neurons that are arrayed in parallel In tissues such as the cerebral cortex, and we have a name for that. We call this gray matter. So as we begin to look into the inside of the human brain I'll be highlighting for you various divisions of gray matter. Those are distinguished from white matter. And now, we can think about the cellular components that help us define what exactly do we mean by grey matter and white matter. So grey matter is where we find the cell bodies, the dendrites and the synaptic connections of neurons. White matter is the conducting zone, that's where we find axons and the special insulation forming cells that surround those axons called glial cells. Specifically in the brain the oligodendrocyte. So that is another component of white matter. And then of course, both grey matter and white matter require nutrients in the form of vascular supply. So there are a vascular endothelial cells in both kinds of tissue. Both grey matter and white matter. And then, finally, let me again emphasize that, where we find the output zone of one neuron, we find the input zone of many others. So, grey matter is both input zone and output zone, depending upon which neuron we have in mind. Okay. Well, enough illustrations, let's look at some actual brain cells. So, here are some pyramidal neurons in the cerebral cortex that I prepared myself. And what we're looking at is a stain that shows us beautifully. A pyramidal shaped neuron here. There's it's cell body, sort of a pyramid looking, something like that, and a thick, stout apical dendrite progressing off towards the surface of the cortex, which is out here somewhere. Here is another pyramidal neuron and it's thick apical dendrite. We also see some basil dendrites extending out away from the cell bodies here. Now, we also have an axon. At least one that I can recognize. And it is this process right here. It's extending away some distance away from that cell body. So that's the means by which this particular cell is going to generate electrical signals and then propagate those signals to its neighbors, some quite near. And then some at a great distance away. Here's another pyramidal cell in the visual cortex, but we don't see it's apical dendrite because we're looking down from the top, so it's apical dendrite is actually right about there. And then here's it's cell body. And from it's cell body are all these beautiful, branching basal dendrites. Now, if we look very closely at these dendrites. And I know this image is not quite as clear as we would want it to be. We can see some spines on these dendrites. In that region and here again down there. So, if we have a careful look at one such area I think you'll be able to appreciate that there are, in fact, some small little mushroom shapes, some filaments that are extending away from those dendrites. And so this would be an example of a typical pyramidal neuron that grows numerous spines along. It's, basal dendrites as well as on an apical dendrite, but typically, a little bit further away from the cell body. Okay, here's another view. Had a, a large collection of pyramidal neurons. And we can see, again, their cell bodies. There are little pyramidal shapes here, apical dendrites heading towards the surface of the brain and then lots and lots and lots of multipolar basal dendrites going off in all different directions. Now, we also can detect the present of axons that are coming out and extending down into this white matter. That's what all these thin filaments are that we can recognize heading down through this relatively unstained background tissue. So, here we see all the various components of the functional anatomy of a neuron, the dendrites, the cell bodies, the axons. Well, we can't quite see everything because we haven't yet seen the synaptic terminals. And to give you a sense of that, I want to show you, you've got a different view of brain tissue. So this is tissue that's stained with a green dye that has labeled axons as they make their way through brain tissue, specifically the gray matter of the cerebral cortex. And I would just draw your attention to these little points of light. These little spots that we can see along many of these axons. So, these little points of light are actually places of synaptic contact. Now, some axons, they would grow out a terminal ending, and then there'd be synaptic junction at that terminal ending. Others tend to make this beaded type of structure and that's what we see here along these green axons. Synaptic boutons and they're making what we say en passant or in-passage synaptic connections. So along these boutons there may be synaptic contacts with dendrites out along the sides here. I know I drew them as if they look like they perhaps are spines but they're really boutons because this is an axon not a dendrite. So this is what we see here in these little points of light, synaptic boutons. Here's one last view of neurons and their axons, so we see cell bodies of retinal ganglion cells and axons that are growing out away from them towards the optic nerve head. And these are axons that are going to form the optic nerves that allow the retina to connect up with the brain and send visual signals into visual processing centers in the brain. Now, let's return to some illustrations of different kinds of neurons and recognize some of the various classes of cells that are present in the nervous system. We've talked a fair amount about the cortical pyramidal cell already and this is a great example of what we call a projection neuron. And the reason why we call it that is because, as I've alluded to, it grows out an axon. That can then project for quite some distance within the central nervous system. Maybe hundreds of microns, maybe even millimeters, tens of millimeters, maybe even tens of centimeters depending upon whether the cell is projecting within the brain or whether it's growing out an axon down through the brain stem and into the spinal cord. So projection neurons are called that because they grow axons that project outward away from the cell body over a considerable distance. And these cells often are excitatory, meaning that they have a excitatory effect on their synaptic partners. They make their synaptic partners more likely to generate their own electrical signals. Now, in addition to the long axon that projection neurons send off in a great distance away, I'll just point out as it's illustrated here that the axon can actually give rise to more local branches. That can activate cells that are sitting right next to the cell of origin of that axon. So there are local connections as well as a single axon that projects over a great distance. Now let's look at these cortical pyramidal cells in context. Here to the left we have our illustration of the individual pyramidal cell. And now we can see the pyramidal cell that is present within the cortex itself. So a body, apical dendrite, basal dendrite, and then a long axon. And here are two other cortical pyramidal cells. So this is a typical view of what a projection neuron looks like and where it might be found in the brain. So the pyramidal cell is a projection neuron, it sends axons over considerable distances that have the effect of exciting their synaptic partners. They may also give rise to local collaterals that might just excite their near neighbors as well. So they sort of have a dual function of activation local cells but also cells at a distance. Now in addition to these projection cells, we can also recognize some neurons that send axons over a much shorter distance. Only perhaps 100 microns. Or a few hundred microns. One example is found here. And this cortical stellate cell. So the cell has a cell body, it's typically multipolar, there are dendrites that go off in different directions, and then there is an axon. And that axon may branch over the nearby territory within the dendritic tree of that cell or just beyond it. So this is called an interneuron, because it doesn't project very far at all. So within the same bit of gray matter we can have projection neurons and we can have interneurons. Now the interneurons come basically in two physiological classes. There are those that excite their neighbors. And then there are those that inhibit their neighbors. And they're roughly equally divided with about as many excitatory interneurons as there are inhibitory interneurons. If we look into the spinal cord we can also see examples of projection neurons as well as interneurons. Here's an illustration of a very simple circuit that we have throughout our spinal cord and in the sensory and motor elements of our brain stem as well, and this is an illustration of the knee jerk reflex also known as the myotactic reflex. So we have two kind of projection neurons that are involved here. We have a sensory neuron with its cell body, in the dorsal root ganglia. Associated with our spinal nerves very close to the spinal cord itself. And it has a long axon that runs out through a spinal nerve. And in this case, innervating a sensory structure embedded within the skeletal muscle itself. This dorsal root ganglion cell grows a essential process of it's axon then enters the spinal cord. Now, it's worth pointing out this particular type of neuron to make the following point. This sensory axon is sending signals into the spinal cord. For that reason we call it an afferent neuron sending information centrally. There's another type of projection neuron here in the spinal cord and it's called the motor neuron. It has a multi-polar cell body in the spinal cord and it grows an axon out to the muscle. And the motor axon is sending signals away from the central nervous system to the muscle and for that reason we call it an efferent axon. So get comfortable with this difference between afferent and efferent. Afferent means signals coming in to the central nervous system. An efferent, meaning signals going out of the central nervous system. Sometimes we use these terms to talk about the flow of information with respect to the cell body itself. We can think of the dendrites as being afferent because information is coming in towards the cell body. And we can think of the axon as efferent because signals are going away. Now, we also have within the spinal cord a short axon interneuron. And that's found right here. So this interneuron has the effect of inhibiting the antagonistic motor neuron. So that when our hammer tap hits our patella tendon, the quadriceps can contract. While the antagonistic muscle, the hamstring muscle, is going to be more relaxed. Because the suppressive or inhibitory effect of this interneuron on the motor neuron that supplies that hamstring muscle. Okay, well this concludes our survey of the microanatomy of neurons, as well as a brief discussion of different classes of neurons. I hope it's helped you understand the different parts of neurons, what they look, how they function. So to help you consolidate your understanding of all of this, I'll leave you with just a couple of study questions. Concerning what we've been talking about as the functional micro-anatomy of a neuron, I want you to talk about how does information flow through a neuron. And think about the various parts that are listed out in these response options and go ahead and select your choice. And then lastly, let's take this concept and compound it. And apply it to understanding the structure of neural tissue. Specifically in this case, white matter. I want you to think about what are the cellular components that we find in grey matter and white matter? And in this question consider those components found in white matter, and choose your appropriate response option. Okay, well that concludes our first tutorial. I'm sorry it went on as long as I did. I will try to be more concise in the future, but I hope you enjoy thinking with me about these topics. I know I enjoyed sharing them with you. So on to our next tutorial, considering the non-neural cells that make up the central nervous system. See you next time.
