 Hello, welcome back to the lecture series in NPTEL on animal physiology. So, we are in section 5 with the nervous system. So, one thing I forgot to tell you that there are almost 8 to 10 lectures dedicated for the nervous system, because of the wide control mechanism it executes. So, as of now we are done with the two lectures, where we have talked about the different kind of neurons, the classification of the neurons and how the neurons transmit electrical signals in the form of action potentials and the all or non property of action potentials. And apart from it, in the second class we moved on to the glial cells, the supporting cells or the second type of cells of the nervous systems and we talked about the complete classification of the glial cells and what are their individual functions. We talked about the myelination and few other details about the electrical activity comparison of glial cells and the neuronal cells. So, today what we will do is that we will talk about little bit about the neurotransmitters. I have just introduced the neurotransmitters. So, today I will talk about the classification of neurotransmitter, structure at the neuromuscular junction, nerve muscle because I talked to that there could be connection between neurons to neurons to transmit signal, there could be information to be processed, a neuron sends a signal to a muscle and according to the muscle twitches or move. So, we will talk about some of these small circuits today and from there we will move on. So, let us start the class. So, we are into the section 5, this is the third lecture out of the 8 to 10 lectures which are dedicated to this section. So, first thing I will do is we talked about this synapse in the last class, I will again revisit the synapse. So, I told you that the possibilities are there that neuron may form synapse on another neurons or it may form on muscles. So, historically speaking the first of the synapses which were kind of discovered and people understood the most where between the nerve and the muscle which were the neuromuscular junction. So, we will take that example. So, I am putting the muscle in greens for example, this is the muscle in probably in the last class what I will do in the sorry in the next class what I will do, we will talk more about the muscle structure and everything that will help you to understand some of the features out here. So, this green color is the muscle and these are the nucleus of the muscle, this is the connection where. So, let me highlight the connection in a red. So, these are the zones where synapses are formed electrical connectivity have formed. Now, if I blow up this picture it will be something like this. So, let us move on to the next page let me blow up this picture. So, it will be something like this I will talk about what are these invaginations and everything and imagine the other side. So, in this case it is muscle and if it is the neuron that it will look like something like this another membrane out here. It could be a neuronal membrane here I am drawing the neuronal membrane it could be a muscle membrane if I just continue. So, what exactly is happening? So, I have already shown you that electrical impulse reaches all the way to the end then what happens this is the most important part. So, few specific terminologies this gap is called synaptic cleft synaptic cleft this is the small gap between one neuron and another neuron or between one neuron and their target tissue which may be a muscle or something else and I express you guys go through the nodes and just check what is the nanometer difference between the two it is a very small gap and this is one exercise I wish you guys carry out. So, in this zone where the axon is making synapses there are lot of mitochondria these are the mitochondria these mitochondrias are power generator or energy generator of the cell there are enormous amount of mitochondria out here. What the electrical signal does when the electrical signal reaches here say for example. So, I told you that there are several kind of neurotransmitters and one of the very widely red neurotransmitters is called acetylcholine. So, soon after this we will come to the classification of the neurotransmitter, but before I go to the classification just assume that this is a neurotransmitter one of them is acetylcholine. So, that will help me to explain how the synapse really functions. So, once the electrical signal reaches out here the next thing happen is this electrical signal leads to entry of calcium ion from outside and in this zone what you will see you will see a lot of vesicles like this and these vesicles are filled with likewise these vesicles are all filled with neurotransmitters these reds are the neurotransmitter molecules in this. So, these the closed ones are the vesicles. So, ignore the one I have just drawn slightly in advance I will come to that. So, look at this synaptic left. So, there are two options the electrical signal may jump to the next one through gap junction we have talked about that in the electrical synapse, but in this case that is not happening in this case there is a physical gap. So, you have to realize. So, this is the basic difference between an electrical connectivity and a synaptic connectivity there is a physical physical gap in the range of nanometers. Whereas, in the case of electrical synapse if I have to draw it just side by side it will look something like this if this is the upper one and this is lower one the one which is receiving there are physical tubing between them likewise this is what is in a electrical connectivity through the in the form of gap junctions. Whereas, in the case of synaptic cleft there is a gap. So, now the red color what I showed you the electrical signal is reaching this is the electrical signal which reaches as the electrical signal reaches at the terminal there is an entry of calcium ions these calcium ion leads to couple of events which takes place here these vesicles they bound to this membrane. So, you see that these look at these vesicles they are bound like this and now you recollect back you remember I in the beginning of the transport phenomena and membrane physiology I taught you people about exocytosis and endocytosis. I told you one of this process helps you to you know throw away something outside the cell throw away. So, what happens this membrane this vesicle which is form of a small membrane this vesicle binds to the master membrane which is. So, this is filled with neurotransmitter and imagine the membrane underneath where it is binding. So, it is binding to this membrane like this. So, next thing what happens these two membrane merges which two membrane merges like this part of the membrane and this part of the membrane they merges and what happens eventually is something like this well they are merging there almost there. So, the next thing what you see is that mind it and this is all filled with neurotransmitters. Then this opens out on the outer side like this and this happens in pico or femtosegans range and these neurotransmitters are given out into that cleft. This is the next step what happens now if you follow this what is happening out here now. Stage two this particular cleft soon is filled with all the neurotransmitters. Now, these neurotransmitters once they are into the cleft and in this case we are assuming this these all these rates to be acetylcholine acetylcholine. Once these neurotransmitters are in the cleft the bind to the target membrane it could be a muscle it could be another neuron or whatsoever. So, once they start binding along this. So, you see them all of them like on top of these red lines or you know all over this surface and as soon as they bind they open up a series of cation channels and in terms of from the outside to inside if something has to move. So, this leads to the opening of the cation channels and this promotes the entry of sodium inside the cell in a plus in a plus in a plus from all over the place and mind it this is happening in a femtosegans or a pico second time interval this is very fast. So, these neurotransmitters bind and if you have a confusion out here that I have drawn these on the surface. So, these are on the surface mind it these are not inside the cell inside the receiving cell they are all on the surface. So, if you have a confusion you can rub these off. So, that you should not have any confusion out here that these just for your better understanding let me redraw this. So, they bind to the surface of the membrane and opens up the cation channels and all these cation channels lead to the entry of sodium and as the sodium enters. So, mind it this cell is setting at say minus 75 millivolt negative with respect to E m the membrane potential is minus 75 millivolt minus 75 with respect to the outside. So, as soon as there is the entry of these sodium ions from minus 75 it starts to shoot towards the positive direction and as soon as it reaches something around minus 40 millivolt it shoots up an action potential. So, now from one action potential which was generated out here this action potential is transmitted to the second neuron and the second neuron again carries the same process and wherever it diverges and whatsoever it does. So, still the story is not complete story is not complete because what is happening to these red molecules which are bound out there because if they are bound the next series of signal which is going to come what will happen to that because those neurotransmitters which will be ejected out from the sender neuron would not find a place to bind to the the one where the message has to be sent and just to for the technical terms the one which is sending the signal is called pre synaptic and the one which is receiving the signal is called the post synaptic. In the case of neuromuscular junction muscle surface or the muscle membrane is called the post synaptic membrane and this whole phenomena is called the synaptic event and this is the you can say the central one of the central theme or the central procedure because the way I am drawing it is very simple but think of it when this was discovered this was this was something one of the most part breaking discoveries of discovering synapse in the biological system and for last 70 years people are rigorously researching upon the structural details of this and the features and everything using electron microscopy patch clamp electrophysiology intracellular electrode extra cellular electrode and a whole series of bioelectrical techniques are being employed to understand field effect transistors and likewise. So so what will happen to these neurotransmitters which are present here these neurotransmitters have to be removed immediately otherwise the next signal would not be able to do and these are again I am repeatedly trying to tell you that this is all happening in a picosecond femtosecond femtosecond level domain. So what will happen is that now let us do bit of a small chemistry out here what is happening. So let us make this diagram little bit more simple so that we can appreciate what is happening out here and just make the synaptic cleft slightly bigger because I have to put some of these features out there. So now imagine this vesicle has given the neurotransmitters send out this acetylcholine out here so simplistic only one vesicle bind to it. So what will happen to this acetylcholine is so here you have the the stick of a bigger molecule imagine this is an acetylcholine molecule a single molecule I am just blowing it up now. So what will happen there is an enzyme which is present in the synaptic cleft and that enzyme is called acetylcholine esterase this enzyme immediately come and what it does is it splits this molecule into two parts one is called acetate one side is called acetate the other is called choline. So here is your acetate part which gets metabolized and the other one is called choline this choline is immediately taken back by the cell it goes back inside the cell now you see exocytosis while acetylcholine is being given out by the presynaptic membrane into the synaptic cleft now you see another molecule a part of that molecule is taken back by the cell inside the presynaptic membrane. So that is how the choline gets back inside the cell once the choline gets back inside the cell what happens simultaneously I told you that there is a there are lot of mitochondria out here which are the energy rich or the energy producing machinery. So what it does this gives out an acetyl moiety out here acetyl CoA acetyl coenzyme A. So acetyl coenzyme A with the choline moiety coming from this side forming acetyl coenzyme and that CoA goes back to the mitochondria and this acetyl coenzyme now is packed. So this is a very complex process where it is packed in packaging of acetyl coenzyme into packaging in synaptic vesicles and then this stuff comes here and it is now filled with sorry filled with acetyl coenzyme and it comes here and it bounds again likewise and then again it is being sent out. So this whole complex even has to take place in order to ensure and this is all happening at a very very narrow time window and this is like think of it a neuron in the central nervous system is synapsed by a single neuron is synapsed by 10,000 other neurons. So in other word there are minimum if assume that one neuron from one synapse with another neuron so at least 10,000 but actually one neuron from multiple synapse on another neuron. So think of the complexity of information transfer single neuron receiving inputs from 10,000 other sources at one point of time I mean this is something which is unfathomable this is unfathomably complex and one of the phenomenal network where you have thousands and thousands and thousands of such a neuron in the nervous system and they are continuously based on your experience the informations are getting stored in this form of you know electrochemical mode. So it is believed that all your memories all your information are stored in this wonderful zone the synapse this is a region where it is just like the only any something similar to that you can think of is a membrane of a CD or a surface of a CD or a membrane of older days audio tape where you have the scratches taking place well the sound waves are getting stored something of that kind but how this structure persist how our informations are being stored in the system. So we will come to this section with memory and everything while we are talking about learning and memory but at this point what is most important for you to understand is this this is the central very core to the nervous system I mean there are enough detail I can go into it but at this point what I expect you people to understand the very basic fundamental synapse which are present and from here we will talk about before I move on to the classification of the neurotransmitters we have talked about acetylcholine so I will talk about this information processing part in a slightly more detail. So think of it there are multiple options so once again let me go back to the slide to tell you so the information from if this is the presynaptic membrane and this is the post synaptic membrane. So there are multiple options here so in terms of information processing one option is this that this one this sender say N1 I call this and I call this as N2 N1 sends an excitatory signal. So if N1 sends N2 an excitatory signal the signal is getting transmitted but think of it if N1 from here sends an inhibitory signal in other what is an inhibitory signal say for example N1 leads to the secretion of a neurotransmitter which upon binding to the post synaptic membrane leads to the opening of chloride ions or chloride channels. So what will happen so before this I told you the cations are moving so sodium are moving from outside because outside the cell the sodium is higher inside the cell sodium is lower so by the diffusion gradient sodium will gushes inside the cell. But think of the reverse it is think of the another situation say for example instead of acetylcholine there is another neurotransmitter which upon binding say XYZ neurotransmitter upon binding to the post synaptic membrane leads to the opening of the ports which allows the entry of chloride ion inside the cell if the chloride ion enters inside the post synaptic cell or the N2 what will happen so say for example this cell is sitting at minus 75 millivolt. So from minus 75 instead of going up which was happening in the case of excitatory this will go down to say minus 90 millivolt. So the signal which is coming from N1 to N2 will stop there for some XYZ reason or part of the signal will remain part of the signal will get stop or may be at same point of time to increase your complexity of thought this may receive an inhibitory signal and an excitatory signal and based on that it does a computation and it decides what to transfer. So what will happen is this so the excitatory signal minus inhibitory signal or inhibitory signal minus the excitatory signal will decide how much signal will be transmitted to the next neuron. So think of it now just to help you to think more complex imagine here is one neuron sitting and this is receiving at one point of time at one point of time say for example S1, S2, S500, S2, S3, S4. I am not adding those and up to say S10,000 and S stands for signal at one point of time at time t at time t this cell is receiving 10,000 inputs 10,000 inputs could be excitatory could be inhibitory could be silent could be anything and everything which we do not know based on that in a fraction of a moment this cell makes and complete algebraic addition of this signals and that is what we call as neuronal computation it does all this all this computation with all this and all this all this different signal and decide a lumped up signal what has to be transmitted. So the output signal is decided out here output signal this output signal decides wherever it sense it senses to the muscle sense it wherever x y z target organ decide what is to do it is that level of complexity we are dealing with the best computer in the world the best computer the best super computer what we call that can never ever match this complexity because another important thing if a computer has to do this much calculation the amount of heat it is going to generate it will be enormous but when the brain does this computation it does not generate heat it functions in a totally different way. So in other word you can call those were for electrical or have some bend this is the classic situation of low power electronics where everything happens at a very very low power and this is very very very important for people to appreciate. So this excitatory the number of currencies are very few so this is one way to you know look at it now while I was introducing you there is excitatory and inhibitory neurotransmitters. So think of it that is another way of classification or which adds up adds up to the complexity of this whole procedure that whether it is inhibitory whether it is excitatory what kind of neurotransmitters so that is why we have to come to that classification of a neurotransmitter classification next I told you at delta time t all these things are happening but think of a situation where say for example I have the time t 1 second t 2 second t 3 second t 4 second t 5 second or even less than a second maybe femtosecond or picosecond the signals are coming to this to this target. So there will be a different kind of addition that is called so if this one is in the same space in the same location they are all coming at the same time same time mind it all the signals are coming at say now all the signals are coming likewise that is on this part so that is called spatial summation. Summation is only a function of a space spatial summation whereas think of the another situation where signals are coming like this over a period of time so it means my is a signal likewise these are the signals so they are coming over a period of time so those kind of signals what happens say for example think of this situation one signal so all the signals are coming at the same time on a target this leads to a spatial summation now think of it here is the base t so that y axis x axis is time here is the time so signals are coming like this or maybe you know different amplitude different magnitude different time window so and your y axis is a signal amplitude of a signal so if this is a temporal this is a spatial summation spatial SPATIL spatial summation this one is called temporal summation this is even much more complex so 10,000 inputs over a period of some few femtosecond or a picosecond or a nanosecond is coming think of it so this is the level of complexity a nervous system harbors it is a very very complex and it is a very very interesting system that is why as they call it that our next code so we know in biology there is something called a genetic code where we know the how the genes demonstrate a function or a protein or our phenotype now the next code which will be the next frontier on one of the very profound frontier will be the neural code what we mean by neural code this is something very important for you people to appreciate before we go in depth with the nervous system so say for example someone must have taught you someone must have told you that this is a cell phone this is a cell phone who taught you this is a cell phone you saw this and you figure out so if you see another cell phone like this you will say oh this is a cell phone I know this is a cell phone fine so whenever we tell that this is a cell phone now let us take another example this is say for example a notebook we call this is a notebook so somebody must have taught you that this is a notebook so what I meant by that or say for example I say oh this looks like a pen or say for example I am a mic here so by looking at it I can say oh there is a mic so this is very important if I call I never call this cell phone as computer or a cell phone as calculator I never call this notebook as something say stool or something I never say this why I do not say this because this is very important for so my system whenever I look at say for example I have an apple out here so for example I have an apple out here while we were small kids someone has taught us that this is an apple and if this is an apple then it has a neural code it has a neural signal which is a stored in your system as an apple whereas if you see say for example mango so this is a kind of a people writing out of mangoes nowadays so somebody must have taught us that this is a mango and it has a different kind of signal same way everything what we see has a correlated neuronal code and that code teaches us that this is a mango this is an apple this is a cell phone this is a book this individual is your mother this individual is your father this individual is your sister this individual is your friend this individual is your wife so there are informations which are stored in the system so if some way or other I know I know that this signal is a signal for apple now say for example somebody does not have an eye who is blind and if I could feed into that individual's brain that this is the signal of an apple the person should technically should be able to visualize that in other word could we use could we see a song you understand what I meant that this means like this if this is your brain this is your brain and it has different areas which is a storing different kind of information so there are visual areas there are all factory areas which you can smell there are hearing areas where you hear where the sound informations are being coded so these are the different areas of the brain say for example so let us take the example of this say for example this is the say I call this as a visual area so in terms of the visual area I told you that there are signals which says that this is an apple fine this signal is for an apple now if imagine this is a sound area where sounds are decoded after all end of the day that is nothing but an electrical signal which is reaching out here now if I feed this signal the signal of an apple to the sound area what will happen a very fundamental question if I feed the signal of it of the sound of the apple of an apple that electrical signal to the sound area could we hear an apple I may sound very bizarre I may sound very like you know am I mad to tell could I hear an apple but think of it that is what exactly I want prompt you guys to think that could I hear an apple could I see the sound because in the visual area I am feeding a sound signal something which is sound could I see the sound because as of now you are hearing me you cannot see the waves could I see the sound could I hear the apple these falls under one of the most beautiful and challenging area of nervous system called neuronal code what are those codes which ensures that we identify our parents we identify the roads to which we are travelling because errors in those leads to dreaded disease like Alzheimer's disease some of the disease like Parkinson and will come to those what is dementia and all other aspects of so this is called the neural code so coming back so there are couple of more things we talked about the spatial summation we talked about the temporal summation now we will talk about another set of summation where say for example information are coming see these are neurons they may converge at a point or what may happen is a signal coming and it is getting you know split up into likewise these are called divergence circuit what you see here the signals are getting diverged one signal or it could be a convergence circuit out here so this is convergence and this is called divergence so this is another mode by which signals are getting computed say for example one unit signal comes from here two unit comes from here they may add up to three unit or there may be inhibition of road server so for example 50 unit comes from here and you know it is getting divided equally unequally at these different nodes then it may again divide equally unequally likewise and that is how the signal is getting diverged into different networks and this is how it happens because think of it whenever you remember something you do not remember with one feature you have multiple feature say for example you see a building so suppose you have come to this building previously how will you remember the building you remember it is that building is somewhere in this location then you remember whom you met in that building then you remember what was the color of that building then you may remember how was the building smelling so think of it smell of action color of visual whom you met is emotional so all these different things gives you a complete picture of that building so in other word all the informations you are gathering at one point are being discretized into different component a visual component all factory component a sound component a consciousness component an emotional component and then when you recall you recall all of them as one unit or part of it some of them missing some of them you may have forgotten or something and what is forgetfulness why we forget so how we acquire information is the most so if I had to say what are the challenging problem of this century what are those kind of million dollar problems memory what is memory what is learning so we will come in depth into those memory and learning but for now just as I told you that we will talk about the classification of the neurotransmitter let us come to the classification of the neurotransmitter and then we will again come back to this debate neurotransmitters are wide range of chemicals so it may sound bit of a drab to go through this classification but it is really essential so the first one which you have already dealt is acetylcholine acetylcholine second one bigger group is called biogenic amines under this you have nor epinephrine epinephrine then you have dopamine and you have serotonin well talking about serotonin those of you who take antidepressant or something like prozac zoloft paxil they are nothing but all serotonin okay so paxil zoloft prozac is the buyers product okay then you have histamine in that okay then coming to the third one is the excitatory amino acids excitatory amino acids includes glutamate and aspartate I kindly want you people to go through these structures just for the curiosity sake then you have inhibitory amino acids which are opening up the chloride channels inhibitory amino acids which includes GABA gamma the full form is gamma amino butyric acid glycine is a fifth class which belongs to neuropeptides right this is one of the very emerging classes of it substance p and opoids endorphins enkephalins and dinorphins then you have some specific gases one of them already won a Nobel Prize carbon monoxide nitric oxide because these gases does not need any kind of getting they could really go through the membrane as we have already discussed this and other synaptic chemicals like ATP, GTP hormones will come to this okay and something like prostaglandins okay so for example okay so these are the broad classifications of the neurotransmitters so after giving you this broad classification of neurotransmitters and as mentioning you about that prozac paxil and all these kind of drugs which are so in other word what does this mean say for example if I have a some way to define say for example let us think of it okay this is the brain and this is the spinal cord likewise okay now if some way or other say for example this is some kind of a circuit which is governed which is governing our you know multiple processes coming through and like you know there is lot of network okay so imagine this is the circuit which I have put in red is dictating that this person is getting more activated whenever this circuit is getting more activated this person goes for a depression in other word some way or other if I could modulate this circuit with some x y z component so whenever we talk about depression or you know high or anything you know what does that essentially means is this in a very simple term if I had to in a very most fundamental term if I had to tell you your depression your happiness your everything lies in this zone this is where all these behavioral traits of individuals are being regulated so if you could modulate this you can modulate several things but to modulate this is a very very challenging task so at your synapses lies that in that particular so coming back where I was was trying to draw the circuit okay yeah so all the synapses which are involved all this pathway are ensuring that this person goes in some form of depression or something okay so this kind of circuits leads to an you are continuously fed with some specific kind of neurotransmitters there so now your option is that either you may oppose those neurotransmitters by some x y z chemicals or if the cases reverse that there is a lack of those neurotransmitters that is why this person is suffering from x y z kind of disease then you enhance the amount of those neurotransmitters and will come to this in terms of Eldopa and the Parkinson and everything okay so this is the overall understanding what I expect from this class for you people to understand that end of the day it is the brain which dictates several things all our behavioral traits all our patterns all our behavior how we react to situations this is all governed by the brain and it is governed through the most simple yet most complex structure called a synapse and the network of synapses and by this time I believe you people must be trying to appreciate that if at one point of time or over a period of time there are 10000 inputs coming to an individual neuron and there are 1000s and 1000s and 1000s of such neuron what a complex super computer are we talking about or not even a computer it is above that it is one of the bionic computation machine which helps us to be what we are it is that complex and that serious okay so with this I will close on this class and we will come to the next class where we will be talking about the neuromuscular junction in depth about how the electrical signal is being translated into a mechanical signal so before we start that what we will do we will talk about the structure of the muscle so then the next class we will talk about three circuits we will talk about reflex circuit and what is the reflex circuit we will talk about the neuromuscular junction we will talk about the how the electrical energy is translated into mechanical energy okay thank you guys for your attention.