 Welcome back to the NPTEL lectures on animal physiology. So, in the last class, we started with the section 5, where we started with the nervous system. So, the first lecture on the nervous system, we dealt with the structure of the neuron, the way action potential is being generated. And we talked about how it is getting transmitted, because of the voltage gated potassium channels, voltage gated sodium channels, especially the voltage gated, fast activating voltage gated sodium channels and delayed rectifier potassium channel. So, today I will just take a slight detour, because coming to section 5, this is nervous system, this is lecture 2. So, what we will do today? So, if I go back, so this is what I showed you. So, the signal comes like you see, if you see the signal is coming here, signal is coming here and then this is getting processed and then signal transmitted and it moves on to the next target, which will be a neuron 2 or neuron 3 whatsoever. This is how the signal or the messages are being transmitted all along this path. It moves like this. So, at this point, I will highlight one more thing. If you remember, while I was drawing the structure of the neuron, I told you that there are some neurons, which are like this. This is the terminal, where the message is being transmitted to the next neuron. This is where the message is being received by the dendrites. So, we talked about that some of the neurons have an insulated covering like this, which is called myelin sheet. If you go back to the lectures, let me see if I have the, let us see which one is the one, where I talked about the myelin sheets. Yeah, look at this. This is the myelin sheet, what I was telling, what I am trying to tell you. Now, what is this myelin sheet? This is where comes, if I go to one lecture even further back. In the classification, we did not talk about, as of now, about the neuroglia. What I will do before I come back to the nervous in electrical impulse transmission and the synapses, I will take a slight detour and I will talk about the neuroglia and how this neuroglial cells are involved in formation of myelin sheets and all other things. So, let us go through and move on to our current lecture, where we will be talking about the glial cells. So, we will start with the glial cells. So, in the nervous system, we started with there are two kinds of cells, the neurons and the glia. Neurons are of different types based on their position, they may be in the peripheral nervous system, they may be in the central nervous system, they may be in the specialized sense organs, whereas the glia too has a wide range of classification. They may be in the central nervous system, they may be in the peripheral nervous system based on their functions, they have a wide variations, what we are going to talk about it. But, broadly speaking, till 2013 when we are at this point, it is as of now also believed that most of the communication major electrical signal transfer is taken care by the neurons. The glial cells are the ones which modulate those signals, but all by itself glial cells as of now has not been seen that could govern a circuit, they are modulators. It is just like say for example, there is a circuit, you have certain capacitors which store charges, you have resistors which act as a current flow stopper, they create resistance against the current flow. Likewise, the glial cells are the ones or you have like heat sinks which removes the excess heat from the IC chips. The same way, the glial cells are the supporting very vital supporting structures, but do they involve in direct electrical communication and they do they involve in a information storage is still a very debatable issue. There is enormous research taking place across the world, there are some well-renowned glial biologists across the world who are extensively working to figure this out that what are the final and maybe in the next 50 or 100 years, we will come to lot more about the glial cells, but for now let us do the classification of the glial cells like this glial cells and sometimes this is also called neuroglia. Neuroglia is classified into two broad classification, the one which are present in the peripheral nervous system just the same way as the neurons, the one which are present in the cell nervous system. Within the peripheral nervous system, you have the Schwann cells stage and we will come at this point just note down all the names, you have the Schwann cells and you have the satellite cells. Within the central nervous system, you have oligodendrocytes, O L I G O D E N D R O C Y T S oligodendrocytes, astrocytes, you have microglia. Now, what these individual cells are the role to play? So, we will take up these two cells first the Schwann cells and the oligodendrocytes. Both Schwann cells and oligodendrocytes are involved in myelination coming back to the previous slide. So, this myelination what you see out here what I am shading now this myelination is done by either it could be a Schwann cell or it could be an oligodendrocyte. So, if the neuron is present in the central nervous system it is by oligodendrocyte, if the neuron is present in the peripheral nervous system then it is by Schwann cells. So, is the pattern of myelination the same? So, let us see how exactly it is being taken care first of all we will talk about myelination by Schwann cells. So, in other word we will be talking about myelination in the P N S by the Schwann cell how this looks like. So, here is a neuron a peripheral neuron present outside the central nervous system the endoretic arbor and here you have the here you have the myelination like this. There is a slight gap here the way I am drawing it just do not get let me redraw it one second this is the now let me redraw it you see there is a slight gap I am drawing and there is a reason for that I will come to that. So, this is how the basic architecture looks like within this you have these are called nodes of Ranvier. These nodes of Ranvier are the places where maximum electrical signal is transmitted. So, in other word while I was trying to draw that in the previous slide if you go back to the slide like this the transmission this transmission takes place this is the kind of transmission in an un myelinated neuron there is no myelination. Whereas, in a myelinated neuron like this one or like this one the signal hops like this this is called solitary transmission of electrical signal. And these are the zones if I had to amplify these zones where there is a gap these are very rich presence of voltage gated sodium channel. I am just putting V G as the voltage gated voltage gated sodium channels voltage gated potassium. Sodium channels they are very pronounced in these zones and this is where the major transmissions takes place these are the zones or this is the zone which is called the axon hellock. This is another zone where you will see a very high density of voltage gated sodium channels. So, if you have some marker that you can locate the spatial distribution of sodium channels in an myelinated neuron this is where you will see in most of the neurons in axon hellock you will see a lot of sodium channels out here out here as well as out here. So, this is called myelination result in solitary or hopping electrical transmission or coming back to. So, this is called the nodes of ran via. So, how this is structured this green color structure what you see how it is being formed. So, how it is formed is very important very interesting. So, it is something like this. So, imagine this is the axon hellock. So, what exactly happens in the beginning. So, initially series of cells called Schwann cells which come close these are the Schwann cells these are bipolar cells and these are the glial cells they come close to the axonal body of the neuron once they come close the next thing they do is these cells. So, these cells come close and get on top of these axon like likewise at this stage stage 3 these cells starts dividing on top of each other likewise and in that process they form all the different gaps and everything. Then these dividing cell mass it is kind of what it does it forms an encapsulation all around it goes underneath and it form a complete cavity something like this. This is the part then it forms something these cells eventually start secreting something called myelin protein and they form start forming something like this and this is how the nodes of ran waves are formed. So, eventually what you see if you look at this if you look at this. So, imagine that that this is then this is an axon if this is an axon which is travelling say for example, this is one end the other end. So, this is what happens it forms a wrapping like this. So, this is the wrapping. So, this is the glial cell glial cell mass which forms a wrapping. So, in other words if I had to open this up it looks more like that these are the individual cells. If you look at this structure there are pointed ends out here and it forms a wrapping on top of it likewise. So, this wrapping is this or this wrapping is something like this. So, this cover if you see the cross section of the neuron it will look like this a cross section of the neuron will look like this. If you cut the cross section you will see the wrapping of figure this out. So, the cross section look something like this. So, this is the pen which is pointing out is the axon and this is the wrapping. So, in the back you see this is the wrapping. So, if you draw the cross section it will look like this in the center you will see the axon and on the side this is you will see the wrapping of the. So, this is how it looks like, but is this the same thing which is being followed in the peripheral nervous system. So, this is being done by the Schwann cells. But is this the same geometry followed by the oligodendrocytes which is the second side. In the case of oligodendrocytes the formation of the myelin sheet is entirely different. It follows a very different protocol or a very different root modus operandi while forming the myelin sheet how it works is this. So, what I will do I will make a central nervous system network of neurons and from there I will try to explain this. So, imagine this is the central nervous system network of multiple neurons. For example, these are neurons like this. So, which is a very dense network of different kind of neurons likewise. So, imagine there are just for the simplicity sake I am keeping 3 neurons or maybe I will have few more out here. So, and this is in central nervous system which is much more dense network. So, we will introduce the oligodendrocytes with a different color here at the oligodendrocytes. So, the oligodendrocytes here what it does oligodendrocytes are sitting here much more smaller cells out here likewise. So, these green spots are oligos these oligos are if I have to have a bigger picture of an oligos oligos are something like this very different kind of like they have multiple imagine a neuron without an axon almost like that it is a much more denser structure. So, this denser structure what it does see it is making contact and on the other side maybe an oligos instead of wrapping the cell it forms contact likewise like see these are making contact and these contacts actually act create the myelin sheet likewise. So, it is totally different if you remember while I was trying to explain how the Schwann cells are forming the Schwann cell coating on top of the axon. Here if you look at it the cells are in close proximity with the cell body or the axon or something, but they are only in close proximity they are and they are sending out their processes with these processes creates that insulated layer on top of these axons and the cell body the way you see. Now, the interesting question arises say for example a cell. So, if I go back to one of the pictures which I tried to explain into this picture. So, they are our neurons which from here say for example from the periphery say for example they are moving all the way into from the peripheral they move all the way into the spinal cord and their processes may end up into the brain or. So, what will happen to this neuron think of it will this neuron have because see try to understand the situation. So, this cell is sitting in the peripheral nervous system this is all up to this this is all in the sorry let me this is all. So, this is all in the peripheral nervous system whereas it is entering into the central nervous system. So, will it have a complete Schwann cell myelination or will it have a oligodendrocyte myelination. So, interestingly those cells which have this kind of long processes part of which it is in peripheral nervous system is this their cell body is sitting in peripheral nervous or vice versa even think of the reverse situation say for example a cell is sitting here and not somewhere in the lower part especially the motor neurons. So, these motor neurons are what is they are coming out and the all the way they are reaching to their targets out here. What will happen will this neuron have a oligodendrocyte myelination or a Schwann cell myelination actually these kind of cells have dual myelination. So, what will happen up to this point up to this point likewise they will have the Schwann cell myelination the very moment they enter into the into the spinal cord and the brain they will have oligodendrocyte myelination. So, in other word the very context dependent where the cell is located and this is very very important for you people to understand that depending on the even one cell could have two kind of myelination based on its location and based on its geometry at specific point. This is exceptionally important for you people to understand and appreciate this is what is happening the CNS and the myelination. So, I think that is what I wanted to highlight there are diseases like I do not know how many of you heard about these like you know multiple sclerosis multiple sclerosis MS sometime this being called these are the diseases where your insulated insulation layer of the neurons are being compromised they die out for some x y z reason these are the people who have enormous problem in there you know. So, in other word what is happening there are two bear wears like this you know like one and likewise and there is a kind of a short circuit between the two because there is no insulation layer. So, these are the people who suffers very miserably who suffers from multiple sclerosis and as of now we do not have hardly any cure for this kind of diseases. So, and these are all disease of the glial cells. So, talking about let us come back to the classification we have talked about two component the oligodendrocyte from the central nervous system and the Schwann cells from the peripheral nervous system and we talked about the geometry by which they are forming the myelination sheet from here let us move on to the other classification in that category which includes your glial cells. So, we talked about within the p n s we talked about satellite cells what satellite cells does the satellite cells are the ones which are ensures oxygen delivery and carbon dioxide removal this is one of the major task it does. Then within the central nervous system you have the astrocytes have wide wide role to play and as more and more research is coming up we are realizing they regulate excitatory neurotransmitters like glutamate and we will come to that we will come to the transmission transmission classification and all those things they regulate excitatory they in other road what exactly let me tell you what that exactly means is say for example, this is a neuron this is the cell board this is the axon of the neuron and say at this end it is transmitting signal to the next neuron and it does using a bunch of specific chemicals which falls under the broad category of neurotransmitters neurotransmitters from one neuron to another they are transmitting signals. So, these chemicals have to be regulated very tightly excess of those could lead to disease like epilepsy or other mental disorders whereas, lesser quantity of those could lead to paralysis or something like Parkinson and all those kind of things and will come in depth what that means. So, it has to be very very tightly regulated and how it is being tightly regulated it is being tightly regulated by a series of enzymes and the surrounding cells which are present. So, if you see a network of neuron it is something like this. So, let us draw a simple network. So, here is a network is forming from here the neuron signal goes like this. So, they have the dendritic arbor. So, even within this if you look at it the complexity of the situation a signal may start from here. So, for example, here it may move like this or it may move like this if there is a connectivity between the two and move like this they may come here or it may move like this or it may move like this whereas, the glial cells are all sitting in the surrounding just putting them like this out here out here out here out here out here already we have talked about their role in myelination. So, these say for example, this is the zone this is a very hot zone where basically all the information transfers are taking place like here like here. So, this is the zone where there is a lot of chemicals involved these chemicals have to be regulated. So, one of the key component which helps in regulating these different chemicals are astrocytes. They help in maintaining the homeostasis of the nervous system and the balance within the nervous system and this is very important and we are learning more and more about astrocytes as the research is unfurling some of their most vital and beautiful roles in this area. Then we have another group of cells which are called within the CNS called ependymal cells ependymal cells what are ependymal cells these are the cells which lines. So, let me again take a slight detour for your understanding what is so challenging about the central nervous system. So, in terms of its drug because there is something called a blood brain barrier. So, let me draw it that will make you realize. So, remember in the first picture I was drawing that like if this is the brain and this is the brain stem and this is the spinal cord and these are the ganglions from where central nervous system and peripheral nervous system and all these things are happening. This is how the signals are all the neurons are coming into the central nervous system and coming out of the central nervous system likewise and so on and so forth. Now, this part what you see this whole thing this whole cellular structure or architecture. So, this whole all the cells out here they are not in direct contact with the blood vessels all the blood vessels which are coming close or coming on top of the brain something like this. So, all the blood vessels which are coming out in the into the brain or anything between the brain and between the tissues out here at the cellular level if you have to understand it because this is I am kind of drawing say at the cellular level what is happening. So, imagine this is a neuron in the central nervous system. So, most of the time what we believe is that if there is a cell like this say for example, here is a cell somewhere else the blood vessels are the capillaries are all over this and the capillaries are involved in all kind of you know the CO 2 intake oxygen downloading uploading and we have already studied about this. But in the case of neuron the capillaries are not in the close proximity likewise no this is not how the neuronal architecture is especially in the central nervous in the central nervous system what is there instead is this. So, for example, in the central nervous there is a barrier. So, the capillaries are somewhere out here they are in not in direct contact with the neuron. So, in between there is a layer of another tissue which is filled with a specific kind of fluid likewise and all the capillaries are on the periphery likewise all throughout it. So, this fluidic barrier is called blood brain barrier. So, this is very important this is important for 1001 reasons. So, the major reason is that if. So, what we do what a doctor does you have to see the practical situation a doctor injects a drug either you take it orally if you take it orally it goes to your gastrointestinal tract from there it is being absorbed by the blood vessels or if it has to have a very fast action the doctor does the injected inject the drug directly into your blood vessels fine or the inject the drug into subcutaneous somewhere in your muscles and from there the blood vessels picks up the drug this is how most of the drugs are being injected. So, end of the day every drug if it has to go at any part of your body it has to be injected into your blood finally it has to travel through the blood vessels unless it is some specific on the spot some muscle or something other than that it has to travel through all the blood vessels and the blood vessels while delivering oxygen and taking away the carbon dioxide ensures the drug is delivered at a specific spot of course this is the problem a drug cannot decide which is the specific spot. So, it kind of gets delivered and that is why we see the side effects because a drug goes all over your body say for example I have a pain out here. So, technically speaking I would love all the pain all the drug should come here, but how you could decide that it is not possible because it is travelling all over your body. So, it will keep on downloading and that is why instead a drug which could have actually acted with you know say 5 micro gram or you know 1 pico gram you need to take a pill of say you know 50 milligram why because rest of the 50 out of that 1 pico gram or 1 micro gram or 10 micro gram or 100 micro gram rest of the drug is all over your body and they do some unusual things. So, that is what we talk about you know why we should avoid too much medication because you have other complications because the drug is not needed by rest of the body it is needed by some specific spot. So, there is no localized way of you know telling the drug hey you know what you have to go here because this is where you are needed there is no way. So, this problem becomes even more complex while we talk about the brain why is it so because. So, as of now if you see this diagram it is that will clarify your situation. So, in this diagram you see so the drug is present here. So, the drug is being taken up by the cell which is perfectly all right, but think of it now this blood vessel is not in direct contact with this green cell what will have happened with the situation like this think of it. So, the drug needs a molecule which ensures that it reaches the other side something like a ferry boat likewise and that is why there are very few drugs for central nervous system because the blood brain barrier ensures that your brain or the spinal cord or the central nervous system is not exposed to unnecessary molecules it is very tightly regulated it has to be absolutely insured and that insuring is being run by this barrier and this barrier is made up why I take what T 2 O 2 blood brain barrier is that I talked about the ependymal cells these ependymal cells are forming the lining of the blood brain barrier apart from other cells there are other endothelial cells and all those things on the blood side of it these are formed by the ependymal cells. So, that is why I had to all the detour, but it is good that I discuss this blood brain barrier with people that will help you to realize why a drug because. So, what happens along this if you see this diagram. So, what happens at this zone there are specific boards pretty much a molecular boards which carries the specific molecules there are glucose carrier there are of course, the gases moves through by the simple diffusion, but there are for the glucose for fructose for x y z molecules there is specific carrier which helps them to travel to the other end of the brain. So, your only other option left is that if you want to directly deliver then you have to directly inject something directly to the neuron or that neuronal mass there is no other way a neuron can reach or sorry a drug can reach directly to the neurons till it crosses the blood brain barrier. So, that is the role of the ependymal cells. So, now as I am progressing through you must be realizing that how important these glial cells are and one more in that same line we have not talked about this. Let me get back to that one is the microglia these are microglia these are some specialized cells and there are lot of controversies whether we should call them whether it should be part of the nervous system or they should be part of the immune system because these are the cells which can be termed as the immune cells of the nervous system. What they do is whenever there is a scar or something at some point say some point in the circuit there is a scar or something see this is the scar. So, these microglia rushes to that site and ensures to clean it up it is just like on the road there is some form of accident or something. So, as soon as there is an accident very soon there are convoys which come which ensures that you know clean up all the stuff from there. So, that the traffic can move on. So, it is exactly what microglia does it is the cell series of cells which comes there and clean up all the chemical debris the eat away everything and ensures that the traffic is continued and at times they even form very specialized structure out there and will come to that in spinal cord injury and all the things. So, in order to summarize what we talked about the neuroglia. So, we talked about neuroglia could be on two sites in the p n s as well as in the c n s within the p n s they could be satellite cells which are regulating carbon dioxide and oxygen. And there are Schwann cells which are forming the myelination sheet on the c n s side of the oligos which ensures the myelination process in a totally different fashion as compared to the Schwann cells. And you have the astro sites which regulates neurotransmitters and few when several other things it is it helps in the homeostasis of the nervous system and they are in huge number. And then you have the microglia which are the immune cells of the nervous system and then you have the ependymal cells which are forming the lining of the lining of the blood brain barrier. So, these are some of the very important aspects of the glial cells and one more thing glial cells are the dividing cells of the nervous system and neurons do not divide. Of course, there are some controversies here we will come back to that while we will be talking about some of the diseases do all neurons do not divide or there are some neurons which is the ability to divide. But quote unquote it is just we will come to this because there are some specific type species where a group of brain neurons do divide, but they are very specialized cases studies especially in the canary birds and few other biological systems where they do divide and we will come back to those while we will be talking about the different diseases and deviation from the what we see normally. There are deviations indeed. So, whenever you hear about brain tumor or something it is basically uncontrolled division or brain cancer or something it is basically uncontrolled division of the glial cells because the neurons do not divide. So, it is the unregulated unchecked division of the glial cells which leads to any form of brain cancer or brain tumor or any other those kind of diseases where the cell division control or the check points are being compromised and we land up with troubles. So, from here I will come back. So, this was the detour I wanted to take before I move on to the next slide where we will be talking about the synaptic activity. So, what is the synapse? So, this is where we are going to concentrate now. So, if this is a neuron and this is the axonal end and this is the second neuron out here sitting here or it could be any other target tissue as a matter of fact it could be a muscle. So, let us draw that also. So, neuron here you have the muscle. So, this junction what you see out here this junction these junctions where the information are being transmitted or this junction any other such situation these are called synapses. This could be between neurons to neurons or neurons to the target tissue it could be muscle. So, this contact is called neuromuscular junction or neuromuscular synapse neuromuscular synapse neuromuscular synapse and these are called normal regular synapse. There is no such term called regular synapse, but these are just the synapse. So, synaptic activity could be electrical as well as chemical. So, what we meant by electrical and chemical? So, electrical synapses are very rare and very few in the body electrical synapses means say for example, here is a contact point. So, between the axon terminal and the dendritic part. So, if I amplify this. So, this is the axon terminal out here and these are the receiving dendrites out here. So, this is where the synapse is forming. So, between these if I further blow it up between two processes there are gap junctional connection the electrical connection which allows the flow of information, but such information flow is a very local information flow something what you see in cardiac cell it is in within a very enclosed structure where all the cells are you know transmitting. But when we talk about a nervous system which has huge network within our body these electrical synapses are not very successful and they are very very few and very located in very specific areas of the brain the basket cells and some of the I think the purkinje cells they have those kind of synapses, but not very many. What is more pronounced is the chemical synapses what is a chemical synapse. So, it is something like this it is a neuron it receives and here is another second neuron which is sitting here moving on. So, here is the signal coming and moving. So, this is the zone where this neuron transmits its electrical signal to this neuron and it does. So, using specific set of chemicals called neurotransmitters. So, this is what a chemical synapse is all about and we will talk more about the chemical synapse in the next lecture. So, closing on this lecture at this point and we will talk about the dimensions of the chemical synapses and what are the neurotransmitter molecules which are involved in it how those are being regulated by the surrounding glial cells and all other things what are the enzymes which are involved in that whole process and how the informations are being collected converge or diverge and all those things we are going to talk about. So, thanks a lot thanks for your attention.