Transcribed by Tina Park

Friday, January 24, 2014

Neuroscience Lecture 11 Nervous Tissue 1 by Dr. Jean-Pierre Saint-Jeannet Slide 16 A- Neuron Dr. Jean-Pierre Saint-Jeannet Alright good afternoon everyone. So we are going to continue this lecture of the histology of the nervous system. Yesterday we talked about the general organization of the nervous system and then we started to look at the composition of the nervous system the different cell types found in the nervous system. We talked about the major cell type, which is the functional unit of the nervous system, which is the neuron. There are also associated cells with those neurons, which we will talk about also. We talked a little bit about the neuron. We talked about the cell body and some of its characteristics. We talked about the axon. Slide 25 A- Neurons: 1- Functional components: c- Dendrites Dr. Jean-Pierre Saint-Jeannet Now we are going to talk about the dendrites and some of the specifics. I think we left off here yesterday. Dendrites are short branched projections that can form a pretty extensive dendritic tree in some form of cell type. They will be involved in sections of external stimuli and they will convey the information to the cell body. Typically those dendrites contain nissl bodies. If you remember, nissl bodies are sacs of rER that are found in the cytoplasm of the cell body. Those nissl bodies extend all the way into the dendrites. If you remember also those nissl bodies are excluded from the axon and excluded from this region here, which is known as the axon hillock. So we found that nissl bodies number of organelles including mitochondria, and those dendrites carry small protrusions, which are known as dendritic spines. Also known in some textbooks as gemmules. And this here is a specific stain that has been used to visualize those dendritic spines at the surface of the dendrites. So you have a few dendrites here and then green highlighted those protrusions corresponding to those dendritic spines. Slide 26 Image: section of the cerebellum (silver-stained preparation) Dr. Jean-Pierre Saint-Jeannet This is another representation. This is a silver stain of neuron here showing you some of those dendrites and some of those protrusions at the surface of dendrites. So those dendrites, hm. Yes. So those dendrites and those protrusions here, the dendritic spines (theres one here and another one here) will be in fact the point of where the contact between the terminal arborizations of an axon when it makes contact with a dendrite. The synaptic connection will be made at the level of those dendritic spines as you can see here. So you have the dendritic spine, here you have the terminal arborizaiton of an axon that is carrying all those vesicles that contains the neurotransmitters that are making contact with those dendritic spines. So they play a very important role in the synaptic transmissions. Slide 27 A- Neurons: 1- Functional components: d- synapses Dr. Jean-Pierre Saint-Jeannet So we talk about cell body, axon, dendrite. Now we are moving at the other side at the terminal arborization of the neuron, which will be involved in the synaptic transmission. And this transmission of input is mediated by this specialized structure that are known as synapses. So there are special junctions that facilitate the

unidirectional transmission of impulse. It always involves the neuron that is known as presynaptic and another cell that can be a neuron or another cell type that is known as postsynaptic cell. Its function is to convert an electrical signal that will be propagating all along the axon into a chemical signal. So most synapses you find in the human nervous system are chemical synapses that transmit the information by releasing neurotransmitters, which are those chemical signals that allow transmission of electrical signals. Although there is also a smaller number of synapses that are non-chemical synapses that are referred to as electrical synapses. And those rely more on the passive diffusion of ions between cells. And those passive movements of ions between cells are mediated by structures known as gap junctions. So those electrical synapses are more prevalent in lower organisms. There are very few examples in the human nervous system. There are few examples of those electrical synapses existing in the retina for example. Slide 28 Image: Electrical synapse vs. Chemical synapse Dr. Jean-Pierre Saint-Jeannet So just to show you the differences between those two types of synapses. Electrical synapse here in this schematic representation. So you have the terminal bouton here of the axon. This is a presynaptic cell. Were looking at a higher magnification with this presynaptic bouton making contact with the postsynaptic cell here. And as you can see here, the two membranes are coming very close in positions and there is a passage of ions going through from the presynaptic cell through those gap junctions into the postsynaptic cell. By comparison in the chemical synapse. The distance between the presynaptic membrane and the postsynaptic membrane is much greater. This region, space between the two, is known as the synaptic cleft, and this is the major difference. They are close in position in electrical synapse and this is not the case in chemical synapse. Slide 29 Synapse structure and organization Dr. Jean-Pierre Saint-Jeannet And you are going to hear more about the synaptic transmission in this subsequent lectures of this course that Dr. Schiff is going to give you starting next week. I just want to give you one highlight about the structure of this synapse and the function of this synapse. So three components of the synapse. So the axon here. The terminal bouton is making a connection. The presynaptic cell is making connection with the neighboring cell, which is known as the postsynaptic cell. So you have a presynaptic terminal and the postsynaptic terminal here. In between the space that I already mentioned here where the neurotransmitters will be released is known as the synaptic cleft. So the presynaptic terminals contain those vesicles that contain or are filled with neurotransmitters. They will carry also with them voltage-gated Ca channels. The postsynaptic terminals contain the neurotransmitters receptors that are specific for those neurotransmitters. Also contain ion channels, which are also coupled to those receptors. And they can be Na or Cl channels. In addition to that in the vicinity here of the membrane, on the postsynaptic side on the cytoplasmic side of the postsynaptic membrane is the region you have known as the postsynaptic density. And this is not easy to see by light microscopy. Slide 30 Postsynaptic density (EM) Dr. Jean-Pierre Saint-Jeannet You have to rely on electron microscopy to see this postsynaptic density. Im going to put in higher magnification here. So we are looking here

at two, presynaptic cell and postsynaptic cell here, and this is two membranes that is coming close in juxtaposition. And in between is the synaptic cleft. So the vesicle here in this higher magnification that contains the vesicles that contain neurotransmitters in the presynaptic cell. And here is the postsynaptic cell. So this fuzzy, darker region here that is present on the cytoplasmic side of the postsynaptic membrane is known as postsynaptic density. And it can be visualized only by electron microscopy EM because it is very dense to electron. And this corresponds in fact to the accumulation of receptors and scaffold proteins that are essential for reception of signals coming from the neurotransmitters. And that is the landmark for what is the postsynaptic cell. Is that clear? Slide 31 Classification of synapses Dr. Jean-Pierre Saint-Jeannet Classification of synapses. So we essentially find three types of synapses. And this is uh the names are related to the portion of the neuron that are involved in the synaptic complex. So if the axon makes contact with the cell body it is referred as axosomatic synapse. If axon makes contact with dendrite, in this case dendritic spine as I mentioned is the protrusion you find on the surface of the dendrite. This is known as axodendritic synpase. The third type is an axoaxonic synapse where an axon terminal make a connection with another axon terminal. Slide 32 Image with the three types of synapses Dr. Jean-Pierre Saint-Jeannet This is a different representation. Just illustrate the same three types of axon synapses. Axosomatic synapse, the axon terminal makes connection with cell body or soma of a neuron. Axodendritic synapse, the axon terminal makes connection with the dendrite of a neuron. And finally the third one. the axoaxonic synapse where the axon terminal makes a connection, and synapses with terminal arborization of a neuron. Slide 33 Image Synaptic transmission Dr. Jean-Pierre Saint-Jeannet A few words about the process of synaptic transmission. Youre going to hear more about that in the next few weeks. This is here looking at the terminal, presynaptic terminal bouton here. And here underneath is the postsynaptic cell. Im going to try to divide this process in a number of steps, here 8 steps essentially. So the nerve impulse is traveling along the axon. It arrives at the level of the terminal bouton. The first step in that process as a consequence of the nerve impulse arriving in this region, there is an opening of calcium gated channels leading to an influx of calcium into the terminal bouton. One of the consequences of this influx of calcium is the release of the vesicle that contains the neurotransmitters from the microtubule attachments. So those microtubules, remember that neurotransmitters are produced in the cell body and they will travel in those vesicles along the neurofilaments and microtubules to bring them all the way to the terminal bouton. So the first step is the influx of calcium allows release from those microtubules and the fusion with those vesicles with the plasma membrane. As a result of the fusion, the neurotransmitters are being released into the synaptic cleft. And the process of releasing these neurotransmitters is a process known as exocytosis. So the neurotransmitter is in the synaptic cleft. They will bind to receptors, which are coupled to the ligand-gated channels. The binding of those will allow for the release of either Na ions or Cl ions through the channel into the post synaptic cell which will lead eventually to the

propagation of nerve impulse. So depending on the type of neurotransmitter and channel you have here and the type of ion that is coming into the postsynaptic cell you have essentially two types of synapsesan excitatory synapse or inhibitory synapse. Excitatory synapse, Na ion will be entering the postsynaptic cell. In the case of inhibitory synapse, Cl ion will go into the channel and that will lead to hyperpolarization of the postsynaptic membrane. The last step is that once the neurotransmitters made this binding of the receptors it allowed for the influx of ions into the postsynaptic cell. The neurotransmitters has two options. Either it is degraded in the synaptic cleft or it is uptaken by the postsynaptic cell. In fact 80% of the neurotransmitters that is released in the synaptic cleft is the postsynaptic cell will uptake these neurotransmitters and recycle it. 20% will be degraded in the postsynaptic cleft. And the way that those neurotransmitters are degraded is by enzymes specific for each of those neurotransmitters. One of the neurotransmitters that you may know of, Achetylcholine, will be degraded in this region by an enzyme known as acetylcholine esterase. And this is important because this kind of response from a synapse to a propagation of a signal is a short-term process so you dont want a neurotransmitter to stick around for a long time. So an uptake will take care of 80% of it and 20% will be degraded in the cleft. Slide 34 Synaptic transmission Dr. Jean-Pierre Saint-Jeannet Okay one more time to go over the different steps. So the action potential depolarizes the presynaptic bouton as a consequence there is an opening of voltage-gated calcium channels. This influx of calcium promotes exocytosis of synaptic vesicles and detachment of those vesicles form microtubules. That leads to release of neurotransmitter in the synaptic cleft. The neurotransmitter binds to its receptor on the postsynaptic membrane. This activation of the ligand-gated ion channels leading to hyperpolarization or depolarization of the postsynaptic membrane. And then the neurotransmitter in the synaptic cleft Is either degraded or recaptured. Slide 35 Neurotransmitters Dr. Jean-Pierre Saint-Jeannet So a few words about neurotransmitters. Im not going to go into a lot of detail. You will hear more about that. Im just going to go over a few one. Here. Acetylcholine, which is the major neurotransmitter for neuromuscular junction. Catecholamines. Gamma-amino butyric acid (GABA), which is the major inhibitory neurotransmitter from the nervous system. Serotonine is another inhibitory neurotransmitter. And then small peptides (substance P, VIP-vasoactive intestinal peptides, enkephalines) are also neurotransmitters. Slide 36 Acetylcholine (ACh) Dr. Jean-Pierre Saint-Jeannet Ach - neurotransmitter for the neuromuscular junction. As I said it is a primary excitatory type of neurotransmitter. It signals through specific types of receptors that are known as cholinergic receptors. And the neurons that are using Ach as major neurotransmitter as known as cholinergic neurons. This is the major neurotransmitter for the autonomic nervous system. so it is excitatory but it has also inhibitory effect on cardiac tissue, for example where it is involved in lowering heart rate. Slide 37 Norepinephrine (NE)

Dr. Jean-Pierre Saint-Jeannet NE, neurotransmitter for the central and somatic nervous system are also primary excitatory. Neurons using NE are known as noradrenergic neuron and they will signal through several receptors that are known as adrenergic receptors. Slide 38 Gammaamino butryric acid (GABA) Dr. Jean-Pierre Saint-Jeannet GABA, Gammaamino butryric acid, are major inhibitory neurotransmitter in the CNS. The neurons that use GABA as neurotransmitters are known as GABAergic neurons. And GABA is directly responsibe for the regulation of muscle tone and it plays a role in regulation neuronal excitability and acts somewhat of a moderator of neuronal excitability. Slide 39 Serotonin Dr. Jean-Pierre Saint-Jeannet And finally Serotonin, which is an inhibitory neurotransmitter and is primarily found in the nervous system that is associated with the digestive tract. So this is part of the PNS. This is known as sometimes as the enteric nervous system. So the nervous system that is innervating the digestive tract is very essential to the peristaltic movement of the gut. And this is mediated by this neurotransmitter, serotonin. In the CNS it has various functions including the regulation of mood, appetite, and sleep. Slide 40 A- Neurons: 2- Classification of neurons Dr. Jean-Pierre Saint-Jeannet Alright neurons based on their shape, the extent of their process. And their functions can be classified along those lines. So based on structure and the number of processes that are coming out of the cell body we find three types of neurons that are either bipolar, multipolar, or pseudounipolar. Based on the size of those process, they can be Golgi type I neurons or Golgi type II neurons. And based on functions and you heard already about that already, they can be sensory, motor, or interneurons for those making connections between those two. Slide 41 Structural types of neurons Dr. Jean-Pierre Saint-Jeannet Lets look at some structural characteristics of the neuron. So the first type is the multipolar neuron. So essentially it has this cell body that has one axon and at least two or more dendrites coming out of the cell body. The arborization can be quite extensive like in the case of perkinje cell we will talk about later next week. But if you have at least two dendrites coming out of the cell body or many more, it is referred as the multipolar neuron. Again those dendrites will carry the influx to the cell body and all the way to the axon of the cell neuron. Slide 42 Image: Multipolar neuron (spinal cord motor neuron) Dr. Jean-Pierre Saint-Jeannet So for example for a multipolar neuron, motor neuron of the spinal cord are multipolar. This is here a motor neuron in the spinal cord stained with toluidine blue. This is the axon here and those are the dendrites that are coming off of the cell body. So this characteristic makes this neuron a multipolar neuron. Slide 43 Image: Bipolar neuron

Dr. Jean-Pierre Saint-Jeannet The second type is the bipolar neuron. Essentially one axon and one dendrite coming off the cell body so the dendrite and the terminal arborization carries influx through the cell body and then through the axon. Slide 44 Image Bipolar neuron (neurons associated with sense organs) Dr. Jean-Pierre Saint-Jeannet There are not that any examples of bipolar neurons in the human nervous system. They are essentially the neurons associated with the sense organs, the retina, the rod cell, and the cone cell. And the neurons that are associated with the olfactory motor neurons. So this is here the nucleus of those cone and rod cells. This is the axon and this is the dendrite here that are coming off of the cell body. So here this is the olfactory neurons. The axon is here, the cell body, and this is the dendrites. The dendrites here have a number of extensions that are non-motor cilia that will carry the receptor for olfactory producing substance that you find in the mucous that is lining the olfactory of the nose. That is the only three examples of bipolar neurons in the nervous system. Slide 45 Image Pseudounipolar neuron Dr. Jean-Pierre Saint-Jeannet The third type is the pseudounipolar neuron so you essentially have the cell body and you have a single process that is coming out of the cell body and is split immediately into two. And those two processes are in fact the axon of these neurons. You have arborizatino of the axon here and the arboriation of the other end at the axon here. This is called dendrites but is technically not a dendrite. Right? The dendrite by definition is coming off of the cell body. So this is kind of wrong. This terminal arborizatino here is at that case at the end of the axon will carry the stimulus all the way to the terminal arborization at the other end. The nerve impulse is completely bypassing the cell body. Slide 46 Image: Pseudounipolar neuron(sensory neurons of the DRG) Dr. Jean-Pierre Saint-Jeannet Example of pseudounipolar neuron are the sensory neurons that you find in the dorsal root ganglion. So this is a schematic representation of a spinal cord and this is the DRG here and this is the one single sensory neuron that is represented. The cell body here. The short process here that is split immediately in two. And those two parts are the axon of this pseudounipolar neuron. So the information will be captured on the outside carried through the DRG all the way to the dorsal aspect of the spinal cord. This is a histological section of the DRG where you can see some of the neuronal cell bodies of those sensory neurons and some of those nerve fibers that are coming out of these DRG. And this is another representation just to show that this single process that is coming out of the cell body splits eventually into two that is giving rise to the axon itself. Slide 47 Size type of neurons Dr. Jean-Pierre Saint-Jeannet So neuron as I said can be classified based on the size of the neuron. They can be referred as Golgi Type I neuron. Golgi referring to neuroanatomy that first characterized those cells. So if those Golgi Type I are typically very long axon and dendrites and mediates propagation of influx over long distances. And motor neurons are typically Golgi Type I neuron. Well see in context a number of Golgi Type I neuron and we will talk about it on Monday. Golgi Type II neuron that have short axon and dendrites, short process in general, and are mediating only very local effect. And one example is the

interneuron, which are making a connection between the sensory neuron and motor neuron in the spinal cord for example. Slide 48 Functional types of neurons Dr. Jean-Pierre Saint-Jeannet Classification based on function can be sensory or afferent neuron. Transport sensory information from skin, muscles, sense organs, and viscera to the CNS. It can be motor neurons that send motor nerve impulses to muscles and glands and allows for specific response. And the interneuron, sometimes referred to this as association neurons, make connection between the two the sensory and motor neurons. And those neurons are the most dominant neuron that you will find in the CNS. Slide 49 Image of neurons: sensory interneuron motor Dr. Jean-Pierre Saint-Jeannet This is a representation just to illustrate this point. Sensory neuron. We talked about the interneuron that makes a connection with the motor neuron in the dorsal aspect of the spinal cord allowing for the response. Slide 50 B- Supporting cells of the nervous system Dr. Jean-Pierre Saint-Jeannet So this is about the neuron and like I said yesterday, neuron are like represented like approximately 10 billion of neurons in the CNS but there are another major cell type that are 10 times more abundant than neurons all the supporting cells of the nervous system. And by definition those supporting cells are non-conducting cells that dont have the ability to propagate signals. They are associated with neurons and they provide physical protection and metabolic support to the neuron. And they provide electrical insulation to the neurons. As you will see and I will describe that we will go over that in detail, the PNS and the CNS have very different types of supporting cells in general. Slide 51 Supporting cells of the PNS Dr. Jean-Pierre Saint-Jeannet So the supporting cells of the PNS there are essentially two. The Schwann cells known as neurolemmocytes and the satellite cells. Slide 52 Schwann cells Dr. Jean-Pierre Saint-Jeannet So the Schwann cells are named after the German neuroantomist that first characterized them. Those cells originated from the neural crest and there are two types of Schwann cells. Some that have the ability to myelinate the axon and some that dont have the ability to myelinate the axon. So typically Schwann cells wrap themselves in spiral around a short segment of axon to produce the so-called myelin sheath. So it is essentially the membrane of the Schwann cell that is wrapping multiple times around the axon and on top of itself as it spirals. So if you think about the membranes of every cells. It is lipid layer that contains few proteins here and there. So as a result this wrapping that is taking place all around the axon is going to be very rich in lipid. And this myelin sheath will provide insulation to the axon and provide also electrical insulation to the axon. So here you see, a Schwann cell, the nucleus of the Schwann cell and you can see the different wrapping of the membrane all around the axon. So this is a process that takes a long time that starts around 14 weeks of gestation and the myelinating of the neuron is essentially completed around adolescence. So it is a long process. What is important to note here is that this wrapping here you see here this is one single Schwann cell that is making

one single wrapping of axon sheath around this axon here. You have another segment of myelin sheath here that is provided by a second Schwann cell. Third Schwann cell provides another segment. Fourth Schwann cell provides a fourth segment here. Slide 53 Image: Myelinated axon Dr. Jean-Pierre Saint-Jeannet This is another a different representation. So the process is not very well understood at the molecular level. How this wrapping or even at this physical level how this wrapping is taking place. But everything starts at this one axon being essentially surrounded by in a groove of a cytoplasm of a Schwann cell. So eventually this membrane of the Schwann cell will wrap concentrically around this axon here. So this is here fully myelinated axon. This is an EM view for the region here showing the different wrapping and different dense appearance of the wrapping all around the axon here. And you can see there is virtually no cytoplasm between those different layers of the plasma membrane of the Schwann cells. Again one single Schwann cell makes one segment of myelin sheath around the axon.s o each one of those corresponds to one swchann cell. Those Schwann cells that are, or the myelin sheath that correspond to one Schwann cells that are separated by regions that are known as the nodes of ranvier. And we will talk about that on Monday. So these nodes of ranvier is very essential to allow for fast propagation of an impulse along this axon. So myelinated axon in general, the nerve impulse, is propagating along the axon much faster than a non-myelinated axon. Slide 54 Image: Unmyelinated axon Dr. Jean-Pierre Saint-Jeannet So this is a second type of Schwann cell that I mentioned is the non-myelinatead shcwann cell that will surround the axon. In this case there is no wrapping of the membrane around the axon. Wahts happeing is the axon will be enclosed into one fold essentially of the Schwann cell. You can have one shcwann cell that has multiple axons like this, each one in an individual groove or you have a single groove here that accommadates multiple axons. This is here a scanning electron microscope SEM showing the nucleus of the Schwann cell and here the axons that are present in the cytoplasm, essentially, of this Schwann cell. But again there is no multiple wrapping of membrane of the Schwann cell around this axon so there is no myelin sheath. And one segment corresponds to one Schwann cell. Second segment to another Schwann cell. Slide 55 Satellite cells Dr. Jean-Pierre Saint-Jeannet The second cell types found in the PNS that is non-neuronal cell type is the satellite cell. So those cells are also derived from the neural crest like the Schwann cell. And they form a layer of small cuboidal cell that will surround the cell body of the ganglia. This is the case of the sensory ganglia here. You see the pseudounipolar neurons. That is the short segment split into two. Probably the DRG neuron here. And those individual cell bodies are all surrounded by a single sheath layer of those satellite cells. And those satellite cells also provide physical support and electrical insulation to the cell body present in those ganglia. So on a histology cross-section, those satellite cells are not that easy to see. The most prominent thing you can find on cross-section is to look for those nuclei of those satellite cells. Slide 56 Image Spinal cord dorsal root ganglion (H&E staining)

Dr. Jean-Pierre Saint-Jeannet So this is an example here of a cell body here in the ganglia, DRG stained by hematoxylin and eosin H&E. the nucleus here and the nucleoli in the middle. The cytoplasm. And you can see there surrounding those cell bodies those somewhat elongated, ovoid, nuclei that corresponds to the satellite cell. So obviously this is a cross-section so you cannot see the entire section of the cell body but think about this diagram here [previous slide] showing that those satellite cell are truly insulating completely the cell body. Slide 57 Supporting cells of the CNS (Neuroglia or glial cells) Dr. Jean-Pierre Saint-Jeannet So thats for the supporting cells of the PNS. In the CNS, its , we find totally different set of cells. As the group referred to as neuroglia or glia cells. And they come in four different types. Astrocytes, oligodendrocytes microbial and ependymal cells. Ependymal cells are those cells that line the ventricles of the brain for example or the spinal canal. Astrocytes are those star-shaped cells that will make contact with blood vessels and neurons. Oligodendroctes, they are equivalent of those Schwann cells fro the CNS. They will provide myelin sheath to the axon in the CNS. But they strike a different characteristic that I am going to point out. And finally the microglia that are presented as the smaller ones of those supporting cells. Slide 58 Astrocytes Dr. Jean-Pierre Saint-Jeannet So the astrocytes they are the largest of those four supporting cells. They have this very characteristic star-shape. And they provide physical and metabolic support. And they play an important role in scarring of the CNS. And we will talk about that in the context of regeneration of the CNS. Those are to believe as the one reason why CNS does not regenerate as well as the PNS. There is also some indication that they may have a role in removing excess of neurotransmitter from the synaptic cleft. And well talk about that at the very end of today they play a very important role in the bloodbrain barrier formation because those astrocytes make very intimate contact with the capillary that you find throughout the CNS. Those astrocytes are characterized by the expression of specific type of intermediate filaments, which are only found in those cells and are referred to as the glial fibrillary acidic protein (GFAP), which are often used as a tool to visualize those cells in the CNS. Slide 59 Image of Protoplasmic astrocytes vs. Fibrous astrocytes Dr. Jean-Pierre Saint-Jeannet So two types of astrocytes exist in the nervous system, CNS. One are called protoplasmic astrocytes. Typically they have many projections and relatively short projection that makes this very type of network here. And those are the predominant types of astrocytes that you will find in the gray mater. The fibrous astrocytes have less projections than those and usually that projections are much longer. This is a case here of fibroastrocytes. Although I have been stained for this molecule that was mentioned, the GFAP, glial fibrillary acidic protein. And those fibrous astrocytes are primarily found in the white mater. So you find a little bit of both each but those [protoplasmic astrocytes] are the dominant ones in the gray mater and those [fibroastrocytes] are the dominant ones in the white mater. Slide 60 Oligodendrocytes

Dr. Jean-Pierre Saint-Jeannet Oligodendrocytes like I said are those that produce the myelin sheath in the CNS. So they are the equivalent of the Schwann cells from the PNS. So this diagram here show you one oligodendrocytes that have multiple projections and there are, each one of those projections will provide wrapping around specific areas of neighboring axons. So one of the differences between oligodendrocytes and Schwann cells. If you remember Schwann cell the entire cell wraps around the axon to make one segment of myelin sheath. Here the oligodendrocyte have the ability to make multiple projections and provide myelin sheath segment to the same neuron, for example in this case, two of the segments come from this oligodendrocytes, but also provide myelin sheath to other axons. So typically it is very difficult to see those oligodendrocytes on histology because staining, but more indication typically is to look for the nuclei that stain much darker than cytoplasm. Slide 61 Image Oligodendrocytes Dr. Jean-Pierre Saint-Jeannet So this is an example of a section through the CNS, at level of the spinal cord. So you have one cell body here and another one here. And all those cells here. This is one oligodendrocyte here. The nuclei is very dark and typically the cytoplasm doesnt stain at all. This is a schematic representation of the oligodendrocyte that has been wrapping around the axon here. If you can imagine this is the same cell here. The nucleus is very relatively large and you have the cytoplasm which is much more important than in the Schwann cell that will stain very lightly as you can see here. Slide 62 Microglia Dr. Jean-Pierre Saint-Jeannet So the distinction between Schwann cell and oligodendrocyte are clear I hope. We are going to go back to that when we go over the PNS and CNS a little bit later next week. So the third type of cell that you find are associated with neurons in the CNS are the microglia. The microglia originate from the circulating blood and are involved in the immune response of the CNS. The microglia cells have phagocytic properties. They have the ability to phagocytize particles that you find in the environment. They are the smallest of the glial cells and the nuclei are quite dense and elongated, unlike the rest of the glia. Slide 63 Image: Microglia Dr. Jean-Pierre Saint-Jeannet They are difficult to visualize in the classical light microscope so you have to rely on the expression of specific molecules you find in those microglia. So this is an example here where those microglia here are stained in brown and you see those projections for those and then the surrounding tissue here they are lightly stained in other cell types that you find are in blue. Slide 64 Image of supporting cells Dr. Jean-Pierre Saint-Jeannet So based on shape, staining to visualize shape of glial cells that you find in the CNS. So here again the protoplasmic astrocytes that have relative short but multiple process. Fibrous astrocytes that have much longer processes. The microglia that have star-shaped appearance also. And those oligodendroctyes that are visualized here.

Slide 65 Ependymal cells Dr. Jean-Pierre Saint-Jeannet So the fourth type that you find in the glial cells of the CNS are those ependymal cells that are lining the ventricles of the brain and the central canal of the spinal cord. They are cuboidal to comlumnar. Ependymal, they are not classical ependymal in sense that they do not have basal lamina at the basal aspect of the ependymal rather, and thats true for mostly for the ventricles. Rather they have projections that elongate very deeply into the surrounding tissue. And those cells like I said are primarily found in the ventricles in the ependymal cells of those ventricles that have those elongated basal ends are sometimes referred to as tanycyte. And well talk about those tanycyte in the very last lecture when we talk about the regeneration of the CNS. Slide 66 Image Ependymal cells lining the ventricles of the cerebral (left) and the central canal of the spinal cord (right) Dr. Jean-Pierre Saint-Jeannet So these are two surgical sections through the ventricles and here through the central canal of the spinal cord showing the appearance of those ependymal cells that are some of those supporting cells of the CNS here. So no clear basal lamina here [left] at all and those cells sometimes referred to as tanycyte. Slide 67 C- Blood-brain barrier Dr. Jean-Pierre Saint-Jeannet So a few words about the blood-brain barrier. And I included this in this portion of the lecture because one of the supporting cells of the CNS the astrocyte play a very important role in establishing this blood-brain barrier. So the functional arrier provide a tight control over the passage of substances from the blood into the CNS. So O2 and CO2 and small lipid can penetrate this barrier very easily but other substances such as glucose, vitamins, amino acids, are transported actively through the membrane through specific carrier proteins. But it is essential to protect the CNS and the neuronal microenvironment from any microorganism that may be present into the blood stream for example. And this is established by the formation of tight junctions at the level of the endothelial cells of the vessels. So typically vessels dont have tight junctions in the rest of the body. Thats the only place in the body in the CNS where the endothelial cells carry those tight junctions. Slide 68 Image of blood-brain barrier Dr. Jean-Pierre Saint-Jeannet So this is a schematic representation here of the blood vessel and the endothelial cells here. So the blood, endothelial cells here and here the nervous system itself. So those tight junctions here that are present in the endothelial cells, prevent any organism or bacteria to cross this barrier at all and provide a very important mechanical barrier for the penetration of those organisms. So like I said, this is only found in the vessel of the CNS and nowhere else anywhere in the body and where those tight junctions are forming is this depends on the activity of astrocytes that are present in this region. So the end feet of the astrocytes making contact with basement membrane here of the endothelial cells, and those, this connection are believed to stimulate the production of tight junctions from the endothelial cells. Thereby establishing this very important barrier between the bloodstream and the CNS. Okay that is it for today. I will see you next week, Monday.