 Welcome back to the lecture series on NPTEL on bioelectricity. So, today we are into the 14th lecture. So, in the last lecture we initiated with the simple circuits the primitive circuits of the system. So, we started talking about the stretch reflex arc and I explain you the three major component of the stretch reflex arc, the muscle, the motor neuron, the sensory neuron. Sensory neuron is the one which is carrying the message from the muscle about the change in length and motor neuron is bringing back the message telling the muscle to come back to its original position. So, there are within this domain there are few other small elements. So, the sensory neuron which goes into the spinal cord and conveys the message to the motor neuron. It may do it either by directly synapsing on the motor neuron or it may synapse via a inter neuron. These are series of small neurons which perform a wide range of function in terms of computation at the central nervous system. Now, at the level of muscle there are two components. The one component is the component which senses the change in length or the sensor element. The other one is the actual muscle which is getting stretched and coming back towards original position. So, last time when I showed you the circuit, I did not introduce all those nitty gritty details. So, today I will introduce all those nitty gritty details. So, coming back to the slides. So, this is lecture 14 and let us draw the circuit now. So, this is the muscle which I am drawing in green now. It is the change in length of this muscle which matters and within that muscle you have certain elements like this. These elements are essentially the elements which could sense the change in length. So, they have a special name. Those are called muscle spindle. So, now talking about muscle I have to tell you little bit about the muscle before I could explain what is muscle spindle and what is a regular muscle. So, muscles generally if you go through in physiology or developmental aspect of muscle you will realize muscle development is a very interesting process. What initially happens when the embryo is developing and the all the muscle all our musculatures are being formed it kind of starts like this. So, you have certain specific cells which are destined to become muscle fine those which are destined to become muscle initially divides after division they align themselves kind of in a line and then those individual cells loses their part of their cell membrane and becomes a continuous structure which is called a minor tube. So, say for example just what I am trying to tell you it starts like this say for example, these are individual muscle cells fine or say for example, these are the muscle these are the initial cells which are destined to become muscle fine like this. So, these cells initially starts dividing. So, the division process starts they are dividing now you will see clustering of them they dividing out parent cell to daughter cells likewise same here same here. So, once they divide the next thing they do they align themselves something like this they are aligning themselves as if they are standing in a line as if you are in a morning assembly in a school and you are standing in a line they align themselves like this. Once they align themselves the next thing what happens is that these contact boundaries what I am drawing now these contact boundaries are now merged. So, there is no individual boundary left between these muscles and this is exclusively I am talking about the skeletal muscle. So, essentially what you obtain is a structure like this a continuous structure with all the nuclei of the individual. So, these structures are called these are the smallest functional unit of muscle these are called myotubes and these are called myo or the or the muscle stem cells you can call them they are sometimes also called satellite cell because these are the cell which are destined to become muscle and these are dividing myo sites myo means muscle sites means cell cells. So, this is how the myotubes are formed now then how come this next element which I was trying to tell you this spindles are formed. So, that is something a definite story. So, there are two existing theories. So, let me explain the theory then I will tell you diagrammatically exactly what happens one theory says then when we talk about muscle stem cells there are cells which this time to become a different kind of muscle this is one theory. So, in other word coming back to the drawing if I come back to the drawing out in the slide. So, whenever we talk about this muscle stem cells. So, there may be one of the theory says there may be other kind of muscle cells which are different from the existing ones like this and they attain a different pathway instead of making a myotube like this they form very specialized structure like something like this a spindle shaped structure and these spindle shaped structure has the ability to they are called muscle spindle which is essentially this kind of structures and this muscle spindle have the ability to monitor the change or change in length of the muscle. This is one existing theory it is not really clear there is another theory that other theory is even more interesting it says that the muscle starts developing from the common root there is a pool of cells stem cells which design to become muscle they become myotubes but at the myotube level some of the myotubes. So, at this stage now coming back to the slides again at this stage some of the myotubes go for a different fate and those myotubes eventually becomes muscle spindle. But how exactly this development is going on and of course there is another catch to this game they say that this formation of the muscle spindle is also a function of the neuronal innervation the kind of neuron which so then the blue what you see is the neuronal innervation I am drawing say that this formation of muscle spindle is a function of the kind of neuron which is synapsing on them decides what will be the fate of that particular myotube. So, whatever be the story we really do not know how they originates and how they are formed. But what we know is the first drawing which I draw drew for you people coming back to the slides if you look at it like this. So, basically if I now redraw it it will be something like this. So, these are the myotubes all over the place and within the myotubes there are another series of different kind of myotubes different kind of structures which are these ones they are embedded and the proportion of these muscle spindle is far less as compared to the gross the muscle. So, there is another classification on this that classification is essentially called muscle type if you have to say or myotube type muscle type. So, irrespective of this is so there are multiple ways you can classify the muscle one classification is of course, most traditional classification which is the smooth muscle cardiac muscle and skeletal muscle this is kind of, but there is at the level of myotubes there is another set of classifications which is called intrafusal muscle and extrafusal muscle. So, extrafusal is that bulk structure of the muscle what is present and intrafusal are those muscle spindle like structure which proportionately are very less as compared to the extrafusal muscle. So, now this these are the two elements which becomes the which are the contribution or the muscle component of the stretch reflex arc circuit. So, what now I am now slowly slowly opening up the circuit now if this is the case and now if this is a extrafusal fiber likewise you know and just for your interest to realize these extrafusal fibers are the bulk fiber these individual myotubes form super coil structure among each other and they form fibers myofibers. So, we started with myosites we form myotubes from myotubes we form myofibers and these individual myofibers then those spiral like those inter twinned structure then interact with other inter twinned structure of fibers and they form what you see is your muscle the whole muscle fiber. So, it is a very interesting three dimensional structure of coiling and super coiling which constitute gives you all the strength of all the work you do all your life. So, coming back. So, now we are now dissecting out the individual component among this. So, this is your extrafusal fiber all over the place and within this extrafusal fiber you have these interesting component of muscle spindles which are sitting like this and they are actually spindle shaped kind of structure and these are the nuclei and out here there are multiple nuclei likewise. Now, this circuit first of all here. So, as I told you that it is the muscle spindle which has the ability to sense the change in length. So, now impact falling on this fine that is I am showing in yellow once the impact falls on it what happens is this this muscle length gets changed. So, say for example, if it is a finite length let us assume it has a finite length of l fine l you can put any unit centimeter millimeter whatsoever fine. So, now when the stretch falls this length changes to become l plus delta l. So, delta is the deformation which has taken place in the muscle muscle is stretched now in a stretched condition fine. Now, at this stage what will happen now let us add one more component to this circuit that component is the sensory element component. So, where is the sensory element component sitting sensory element component. So, one more thing. So, the muscle has changed simultaneously this stretch has also changed the length of the muscle spindle. So, if this was initially l. So, it becomes l plus if it is l prime then this become l prime delta l prime this is the individual smaller part of it. So, there is a change. So, this muscle spindle is inner weighted by the sensory neurons like this. And the sensory neuron is like this is the cell body out here is going all the way to the spinal cord. So, now whenever there is a change in signal this muscle spindle senses this change and sense electrical stimuli like this in the form of train of action potential to the sensory neuron. So, this is your sensory neuron sensory neuron enters inside the spinal cord. Once it enters inside the spinal cord I told you there are two options this change in length it has already decoded. So, the message there is a change in length there is a specific train of action potential this change is communicated by a train of action potential. In other word would happen now a mechanical energy mechanical energy is translated into electrical energy mechanical energy is translated into electrical energy first translation first change in the energy formatting. Now, this reaches the spinal cord and as I told you there are two options at spinal cord it may either it may either directly convey this signal to the motor neuron or it can convey this signal through small inter neuron present there are multiple inter neuron present in the spinal cord. So, we put both the situation or actually most of the time it is through inter neuron. So, let us put an inter neuron out here which is innovating which is picking up the signal and this it is conveying this signal now conveyed to the motor neuron out here let us put the motor neuron component. So, here in violet you have the motor neuron. So, here one this electrical signal which came from this train of electrical signal which came from the sensory neuron is now transmitted to the inter neuron. So, this electrical signal mechanical to electrical signal now moves to another set of electrical computation. From this inter neuron this train which is now modified the information has been decoded is transmitted to in the form of electrical current to the motor neuron. So, another level of computation taken. So, look at it in a such a simple circuit another set of electrical signal and this electrical signal is the motor neuron the previous one was in the inter neuron and the first one was in the sensory neuron SN SN is the sensory neuron IN is the inter neuron and last one is the motor neuron. Now, motor neuron out here which is the largest neuron carries the message back to the muscle and this junction is called neuro muscular junction. So, now the electrical signal of the motor neuron is translated again back to a mechanical signal in muscle and this essentially the train of electrical impulse sent by the motor neuron is essentially telling if this signal which was conveyed by the sensory neuron was the signal of plus delta L change in length. And this mechanical signal which is sent by the motor neuron to the muscle essentially tries to tell it minus delta L. So, the first set of electrical stimulus which from the muscle after the stretch and after the increase in a delta L length is conveyed to the spinal cord motor neuron via inter neurons. Now, inter neuron the mass sorry the motor neuron compute the signal and send back a message in the form of electrical impulse to the muscle and tell the muscle that change in length what you had at few infinitesimal t time before this should be retracted back it should be minus delta L now. So, this electrical signal what out here is originating on the motor neuron is diametrically opposite if you have to understand it from this signal which was conveyed in terms of plus delta L and this one is saying minus delta L. So, come back to its original position. So, after this change it will tell you come back. So, that it should be again becomes L. So, this is essentially if you look at it for such a primitive for such a simple circuit this is the most primitive circuit which has evolved through million of years. Even this circuit also has first a mechanical signal 2 i electrical signal then that electrical signal gets modified at 2 different level. And then again that electrical signal after all this modification come back and telling convey it is getting converted into electrical to mechanical signal. So, this is the beauty of biological computation and how you can study we have already talked you can poke an electrode out here you can poke an electrode here. If you can really rebuild the circuit on a chip or you can do it in animal proportions very tricky though you can pick an electrode here you can poke an electrode here several ways you can really measure all the signal you can stimulate this circuit and you can do the measure, but yet there are several things which on this circuit what we have been touched first thing what we have touched let me tell you is how when there is a stretch on the muscle how this change is being sensed or in other word this change in length I told you that there is a change in length in the on the muscle spindle change in the length in the muscle spindle how that information on the muscle spindle is transmitted to the spinal cord. Because I will tell you why I am asking this question because as of now whenever I in the last class I was trying to explain the sign apps and everything I told you something like this it is working like this if this is a muscle and this is a neuron then the signal which comes from here the train which comes from here is conveyed here, but think of it here is a reverse situation happening if this is a muscle spindle this signal is being picked up by if this is a sensory neuron in blue. So, this signal is being picked up out here. So, this transduction out here I am showing it to you in green this transduction how this signal how this change in this length is being conveyed is not clear it is really, really tricky to understand how this information from muscle spindle is transmitted to the sensory neuron it is not yet known there is lot of research going on to understand what kind of ion channels are dictating this phenomena and where exactly the signal is it just a physical change or the stretch and pushmen pull or is it because of this stretch these two structure this integrated structure between the muscle spindle and the sensory neuron is so integrated. So, for example, imagine this is your muscle spindle and this these are the processes of the sensory neuron and there is a pressure falling on this something like this is it so integrated that how that electrical signal is transmitted is still a mystery it is not really clear it is suspected though there are some very specialized kind of sodium channels which are involved, but what are their nature and how they are functioning is a matter of speculation at this stage there is no clear cut proof to tell how this transduction is taking place this is one area which is unknown in this circuit. Because as of now building muscle spindle full flageant muscle spindle outside the system is kind of very challenging there are very few labs who has managed little bit in that area, but a significant work is yet to be accomplished before we really understand what muscle spindles are and if you look back while I was trying to tell you the origin of this. So, this is the thing we really do not know the origin of this muscle spindle, but they are those elements which are kind of biologies if you heard this word MEMS micro electromechanical system. So, these are biologies wonder boys of micro electromechanical devices they are small yet they could translate a mechanical information into electrical information and likewise and at the micron level. So, we really do not know coming back sorry yeah we really do not know how this information of change in length is being conveyed from the muscle spindle to the sensory neuron. Next thing is that what we know of course, there are two sets of motor neurons. So, when I showed you the circuit out here I told you that this set of motor neuron or this motor neuron is coming all the way and you know taking care of your muscle fine, but I told you that there is a change in the length of this muscle spindle too. So, the muscle spindle has to come back to its original position how that is being taken care. So, at this stage there is I will introduce one more complexity to this circuit there is another set of motor neuron those are called gamma motor neuron. And these are called alpha motor neurons these gamma motor neurons simultaneously convey a message which inner weights on the muscle spindle and ask it to reduce its length. So, now I am introducing one more complexity to this circuit. So, this signal which went through the internal neuron is conveyed to the gamma motor neuron. So, now just to make the slide much more cleaner. So, component wise you have let us once again let me put all the components one by one you have extra fusel fiber you have intra intra fusel fiber intra fusel fiber or which is also called muscle spindle you have on this side you have sensory neurons this is the you have inter neurons one or multiple then you have motor neurons shown by M N alpha and gamma. So, for the same stretch reflect circuit what I started in the beginning of this class or in the previous class reflects arc. Now if you look at it there are at least six components you have the stretch sensor in the form of muscle spindle you have the muscle which is executing the job in the form of extra fusel fiber. You have the sensory neuron which is wrapped on the muscle spindle which carries the information translate the information to the inter neurons inter neurons divide the information into two components and one component goes to the alpha motor neurons the other goes to the gamma motor neurons. The gamma motor neurons brings which inner weights the muscle spindle brings back the message that this is the change in the muscle spindle you should come back to its original shape because you have to send the next stimuli whereas the alpha motor neuron tells the extra fusel fiber to come back to its original position. So, let us start connecting all this what I have just told you. So, here is the deal so the first is the here is the impact falling in yellow now back. So, it is this is where the first set of signal goes from here the signal is moving to inter neuron from inter neuron the signal is getting divided into two parts alpha to gamma from here this gamma is telling this to come back to its original shape the alpha is telling extra fusel fiber to come back to its original shape. So, what happened here is delta l plus delta l information this plus delta l information in the form of electrical stimuli is being conveyed to inter neurons. The motor neuron does a series of computation and its sensor signal minus delta l prime that is the change in the length of the muscle spindle and minus delta l which is the change in the length of extra fusel fiber and brings it back. So, essentially plus delta l and or plus delta l prime these are the two set of information which is coded and sent to the sensory neuron and if we really succeed in next 100 years there will be time when these electrical signals in the form of action potential could be deconvulated into the different component of l delta l likewise and all those things. So, when we talk about neural code it is that neuronal signature or action potential signature which travels in the form of action potentials from by translating a mechanical stimuli as mel stimuli hearing of course, that is also translated as a mechanical stimuli or a visual stimuli into electrical signal and what are those unique electrical features is a matter of tremendous contention that what are those features what makes you realize that you know this is mel is of say some specific some rose perfume or some you know jasmine perfume or this particular thing taste like that particular wine or likewise you know these electrical signatures are all. So, basically what essentially I am trying to tell you all these informations are coded within the action potentials with some mechanical signal whether it is a visual signal whether it is a say a taste signal how these are coded is the area which is the next frontier for mankind of understanding something called a neural code and if you look through this circuit what I have just drawn for you people I mean look at the level of complexities which are involved here. So, even at this stage if you look at this what sensory neuron is doing they are so simple basically what you will see in a in a patch clamp. So, if this is a sensory neuron you will what you will be seeing is something like this that is it now how from this you can deconvulate it back and tell this component is saying the change in delta is the change in change in length of say muscle spindle and change in length of extrafusal fiber. Extrafusal fiber these are the questions because that is what it will tell if you put an electrode out here a patch electrode or you know any extracellular intracellular that is the training you are going to get. What kind of mathematical tools you will be needing to decipher these signals that how this process is being actually coded by a neuron which could you know in mathematics I mean basically what you are doing is that you are integrating all this signal in one packet and then you know within the packet which component is for whom and then you are kind of you know it is just like there are lot of letters you know they are in a van and they have to be distributed and the postman exactly knows you know this will go to this will go to this house this will go to this house this will go to this house. How a neuron does that how I mean think of it I mean how beauty it is that at this level if you come back to the circuit on the slide you will see at this level also when it is conveying to it is partly conveying to the two kind of say for example, internal it knows which signal like which one has to be conveyed to which one and from here again they are following the separate path and not only that there is one more thing which I have not discussed of course, we are going to come back on this. So, when this signal is coming at the neuromuscular junction from the motor neuron there is a transduction process which of course, will be dealing as we will be progressing how this electrical signal is again translated into a mechanical signal in the muscle and leads to the contraction of the muscle we have not discussed that will be discussing it. So, what I wanted to kind of get in front of you is the thinking process what you guys need to cultivate to understand this whole area of bioelectricity the way things have evolved the way the electrical signals are changing their features and way are so much information is encoded in those action potentials that is something you just have to not only have to read you have to think over it because there is a lot of thinking involved here because it is on all those waves lies the very core of our existence the very core who we are lies in those waves and this needs immense amount of thinking and speculation and imagination to figure this out and that is why I am kind of putting them instead of really you know bogging down with information I am trying to tell you that see how such a simple circuit you can get the recordings not a big deal there are a whole range of, but to appreciate the bioelectrical signal you need to have your imagination in place you think that wow this is not something such an easy feed this must have taken a million years of evolution to reach to that point where you can code this signals and think of the application if some day somebody could decode these kind of things or say for example something like this I mean if somebody could decode if mankind can do so how easy will be our next generation computers how much informations how much how was the whole communication concepts are going to change because biology store way more information and if our average life is 8 years then for 8 years it kept on storing the information the way it wish to so I will close in here in the next class will resume further from this circuit there are aspect of the circuit which we have in dealt especially with the how electrical energy translated into mechanical energy on the muscle we will talk about it we will talk about the molecular structure of the muscle for the proteins how they are arranged and how their movement brings about the contraction and how the neuronal signal is conveyed to them thanks a lot.