 Welcome back to the lecture series on bioelectricity. So, this will be the 23rd lecture. So, in the last class, we talked about long term potential, one of the models of the memory. And further, I very briefly highlighted the situation of Alzheimer's or Parkinson's amyotropic lateral sclerosis and all other neurodegenerative disorders. And we made a comparison that what happens in the case of Alzheimer's, where you have the loss of the memory, loss of identity. Whereas, in the case of Parkinson's, we talked about there is a loss of motor coordination or the motor activities. So, there is another form of memory, which I highlighted in the last class, but I have not gone in depth. That is called long term depression. So, in the case of long term potential, what happens, there is a very high frequency stimulus, very, very high frequency stimulus. And that high frequency stimulus leads to a change in the network properties, so that the network remain, it gets potentiated and it remains active for a long period of time and during which there is permanent, it is believed that there are permanent changes within the system. But apart from it, there are situations, where you do not get very high frequency stimulus. I was trying to tell you certain situations like you are walking, you are learning certain things in a much more day to day setting, which is you are not very intense into it, which you learned eventually. So, this is something like you are getting low frequency stimulus, you are not really very like you know very much into it or there are situations like you know fear, where you see a very small impulse for a very limited period of time, but that is good enough to resulting in a fear, psychosis in your brain or some kind of anxiety. So, these things falls under the second model, which is called long term depression, LTD. And it was around 1980s, one of the Japanese called Ito, who was involved, was pioneer in starting the work on long term depression. And eventually, there are several people who picked up this model, one of them is Teras Sajnowski. And in Indian context, there is Sumantra Chatterjee in NCBS. These are the people who have explored it further with long term depression. So, essentially if you had to compare that what exactly happened in long term depression with respect to long term potential. So, I will be giving you a handout at the end of the course, where you will have a comparative picture of both long term depression and long term potential. But just for your understanding sake, I will kind of draw the situation, which will give you an idea what essentially is happening. So, coming back, now we are into lecture 23rd, lecture 23rd, we are talking about the long term depression or LTD. So, before we talked about long term depression, let us see what happened in long term potential LTD. In the long term potential, there is a very, say for example, something like this. So, there is a very high frequency stimulus and because of the very high frequency stimulus, at some point or other, the neural activity of a network, if this is the excitable y axis talking about the excitability from this baseline value, because of the high frequency stimulus, it shifted and it reaches here. This is what is happening in long term potential LTD and this is your high frequency stimulus HFS and this is the baseline citation and after a point, this is the new level attained. When both the systems are active, this is how you can show it graphically. I will be giving the handout, which will explain it further, but in the case of long term depression, what is happening is slightly different. In the case of long term depression, what you give is essentially something like low frequency stimulus. In the case of long term depression, you have low frequency stimulation. So, basically, a circuit or a network is receiving a smaller smaller smaller smaller input. So, it is not receiving a huge input, as I was kind of highlighting in the case of long term potential and these are smaller units adds up in such a way that the network becomes active at a much more lesser threshold. So, for example, if this is the threshold where the network functions, for example, this is the threshold, the baseline threshold, this network will start functioning at a lower threshold than this. So, it is going to come down. So, essentially what does that mean? That the circuit becomes active at a very smaller threshold. Unlike a situation, say for example, let us take a practical situation. You are riding a bicycle. You hardly need to recall anything. You know how to ride a bicycle once you have learned it or you are walking on the street. You do not have to decide that you are going to put which leg first and which leg second. So, this is essentially is a situation of long term depression where the circuits involved in this kind of motor coordination gets activated with a very smaller threshold, which you do not even appreciate or understand at that point. That you are actually doing a memory recall, but it is fairly inbuilt almost at a very lesser threshold. Same thing happens in the fear psychosis. Say for example, you have seen kind of a snake at some point and for a fraction of a moment, but that fear has activated a circuit which gets or kind of you know modulated a circuit which gets activated at a very lower threshold of electrical activity. That is exactly the long term depression. So, there are areas in the brain like amygdala, which is involved in the fear psychosis that follows the long term depression model. I believe that this is following a long term depression model. Similarly, all your motor activity cerebellum and further down they follow long term depression. It is interesting the hippocampus to follow both long term depression as well as long term potential, but all these different electrical phenomena what we are discussing are they really happening inside the brain or not is a different question. Most of these studies have been done outside the system where in a controlled slice or a network of neurons these phenomena has been observed. So, in summary if we have to say the difference between long term potential and long term depression is that. Long term potential is a process where there is a high frequency stimulus and that high frequency stimulus leads to make the that particular network hyper active and the output of that network is higher than the base line. Whereas, in the case of long term depression what is happening is that from the base line this also becomes hyper active, but at a much more lesser threshold. It does not need any further high or I mean at a much more lesser threshold it becomes more active just fraction of moment it will become active. So, these are the two key models which ensures our at least it is believe are the major model for memory acquisition and during this process there are certain permanent changes which are taking place out here certain permanent changes taking place here certain permanent changes taking place here and these changes are taking place at the molecular level or that the cellular level changes at the molecular slash cellular level. Essentially these changes ensures that our information gets stored now from here what I will do I will move on to the basic waves which are generated by the brain and their significance. So, in order to save it now by this time you have realized it is a dense network of neurons and they are continuously involved in transferring information or consolidating information or storing information. So, your brain remains electrically active throughout your life. So, during this phase depending on what is the stat what is this what is your physiological status at specific time of the day or night. Brain generates a series of waves alpha waves beta waves likewise and these waves could be detected by placing electrode on top of your head by which you can you could have multiple electrodes you know you could have 64 electrodes set all over your brain and based on those frequencies one can figure out that what activity your doing or how much your brain is active and likewise and this whole thing falls under electro encephalogram. So, let us move on to electro encephalogram EG monitoring brain activity stands for electro encephalogram. Now what essentially is the EG happens. So, for example what you do is that you put place different electrodes like this on the head this is just surface electrode and what you are essentially measuring here you are measuring the these are the electrodes which are placed you are measuring the field potential. So, at one point there are 1000 1000s of neurons and the summation of the electrical activity that is what you are measuring it is a very gross measurement one you cannot figure out what is exactly happening at individuals at the individual cellular level or at individual synapse. What you are essentially getting is a pool of synapse arising from 1000s of neurons at one point and the total summation of that and how that influences or how that could tell you or how you could picture this rate of the brain based on those waves all over the brain. Now what are the different waves which are involved in the brain you have alpha waves you have beta waves and come to the details of all this alpha waves you have beta waves you have theta waves then you have delta waves what these are. So, if you look at alpha waves alpha waves occur in the brain of a healthy awake individual healthy awake individuals whereas very interesting this alpha wave disappears when you are sleeping. So, just and it disappears when you sleep whereas the beta waves are typical individuals who are either concentrating or task or they are in a stress situation. So, just use another color. So, you are say for example you are concentrating or stressed out you see the beta waves then you have the theta waves the theta waves may appear transiently during sleep in normal adult, but are often observed in children and intensely frustrated individuals this is a very interesting kind of situation. Mostly it is seen in children or when a person is very very frustrated you see the theta waves whereas you have the delta waves these delta waves are very large amplitude low frequency waves large amplitude low frequency waves and they are normally seen during deep sleep in individual of all ages. So, if you realize these are the ones which are something like if I had to just draw a comparative picture of the different waves. So, they will be something like alpha will be when the person is awake you know this is what you see as an alpha whereas the beta is even much more like you know this is the intense situation when you are concentrating or you are very very stressed out on something this is the kind of beta waves which are coming and then you have the theta waves which is person is frustrated or you see in the children likewise and then you have the delta waves which are much more. So, these are the delta these are theta this is beta this is alpha. So, these are the four different wave patterns which are being seen in the brain. So, these are the different four patterns which ensures the what state the brain is and how it is kind of you know altering depending on the state of the individual. So, based on this several psychological tests are being done is the nature of this person how intense this person is and the doctors make whole lot of observations on these kind of individuals that which wave are prevalent on which individual and they also highlight a lot of physiological disorders. Say for example, in the case of epilepsy you see huge change in all these things in the case of epilepsy where there is basically a seizure is taking place you see there is a absolute asynchronous behavior among all these different waves and this is something which those who are expert in reading these waves can figure out that this person suffers for is has the tendency to suffer from epilepsy or the wave pattern completely changes over a period at that particular point of seizure or just before that is started kind of you know this balancing. So, we started with in the class about when I talked to you about that you know we will be talking about how to measure electrical signal at the single cell level we talked about how we study the different kind of channels then we talked about how we could pattern the neurons on top of microelectrode arrays how we could use sharp electrodes to make the measurements and here we are talking about electroencephalogram which is on a live animal you are making this field potential recordings. So, all these different kind of recordings had their advantages and disadvantages when you do a field potential kind of measurements like alpha beta theta delta wave you get a gross picture of the brain out is functioning and without any invasive technique it is fairly straight forward and of course these techniques of the waves are being support are being further assisted by the MRI and the positron emission tomography and magnetic resonance imaging they these two other techniques very profoundly powerful technique helps in really picturing the brain what essentially is happening inside the brain at a specific point of time. But they would not tell you anything at what is happening at the cellular level whereas if you come down the cellular level you can understand the phenomena at a single cell level or may be a group of cell. But you have no idea about how the population is behaving at that point of time then you can further go down you can make circuits of one neuron two neuron four neuron six neurons likewise and you can understand the small network behavior. But what is the take home message of this whole process is this whole process are slowly diverging or disclosing those secret stories of our own self why we are like this why our behavior is like this why certain people have sleep related disorder why certain people have hallucinations why certain people cannot concentrate at certain things whereas others can concentrate why certain people gets a stressed out on the other end why certain people does not get stressed out there is series of such things which are highlighted by you know by these different techniques which eventually leads us to understand our final frontier the brain. Now I will give you a very brief very very brief outline about some of the sleep rhythms what is there and we will move on from there. So sleep this is a very very interesting phenomena and sleep related disorders. So when you are so in their deep sleep basically so there are different kind of there is something called a REM sleep and the REM sleep because this is called rapid eye movement sleep this is where you see all the dreams and it is a rapid eye movement it is something like this then you go to the deep or slow wave sleep and this slow wave sleep is the time when the waves are much more you know. So whatsoever dreams you see you see pretty much out here and this is all electroencephalogram recordings and essentially you will observe that deep basically as you are kind of initial phase of the sleep which is basically the REM sleep and then there is a transition phase between the REM and the deep sleep. So from the REM to the deep there is a small transition phase and then you will realize that most of the deep sleep in an average individual takes place between 10 a m to that midnight period it is very interesting and this is where maximum deep or slow waves functions and after that again there are rapid eye movement and likewise so on and so forth. So one of the challenges what we are or we are going to face is we are or we are going to face is we will be needing more and more tools which could couple with the existing tools of MRI, PET, electroencephalogram in order to understand or get a much more holistic picture of the brain what exactly is happening and more and more research is going on in the field of imaging especially the brain imaging to understand some of these very deep rooted phenomena of consciousness, learning, memory, sleep, dream and the relevant disorders. As we will be moving through we will be talking about the man machine interface on a small part we will be dealing with it there you will see how we really could you know house relations and how we could really you know control the brain activity of course not in the human level but at least definitely at the levels of the monkeys I will be giving you a certain hand out and I will discussing that with you. Now I will just take a small detour with this background I will close in here with this part of the sleep and I will come back to one of the part what we talked about about the spinal cord. So, yesterday I talked about Alzheimer's I talked about Parkinson's disease but I what I have not talked about is the amyotropic lateral sclerosis ALS. In the case of ALS what happens is that so I told you in the case of PD or the Parkinson's disease it is substantial nigra within the brain which is kind of getting affected. So, there is a region called substantiated nigra. So, these neurons fail to send electrical stimulus whereas, in the case of ALS what happens. So, these neurons sends the message to the lower motor neurons which are sitting in the ventral horn. These motor neurons when they start to die that neurodegenerative disorder is called amyotropic lateral sclerosis. So, essentially your substantiated nigra is all fine. So, the electrical stimulus is coming from here, but from here what it is supposed to relay the electrical informations to the target tissue is not taking place. So, this is the situation with amyotropic lateral sclerosis and further there are situations when because of accidents or because of certain some kind of mess up basically these neurons is started to die or dies out certain part of the circuit you know kind of get damage which is essentially spinal cord injury which mostly happens during you know automobile accident or some other very hasty situation. So, in the case of spinal cord injury there are several roots I mean one of the possibilities of future will be somewhere or other if you could regenerate those neurons which are kind of damaged at a specific part. You implant the stem cells and they somehow or other get incorporated or you can put a neural chip out here something like you know neural chip which will take care of it or you could have an artificial device which will rebuild the connectivity between. So, it is almost like a fuse goes off you know then this connectivity has to be reestablished or you follow a stem cell therapy or somewhere other you do put certain stimulating electrodes which will help to you know regain or maintain some of the activities. So, there are several techniques at the level of neuro prosthesis. So, this is all regarding spinal cord injury situation. So, there are several techniques by which people are trying to counter the spinal cord injury patients similarly on the same line if you if I go back to the brain say for example, what will happen if part of the brain dies out something like this say for example, out here there are people who are trying to you know implant chips on the brain attempts are going on that if you could implant a chip on the brain at the place where the damage has taken place of course, the other therapy will be you know you incorporate stem cells out there and those stem cells become electrically active. First of all they become neurons and those neurons become electrically active. So, it means whenever we talk about electrically active that means essentially they should be able to you know generate their sodium channels and then they get incorporated in the circuit, but we do not know really if these such cells get incorporated into the circuit how the connectivity will be dictated what kind of connectivity they will establish with the rest of the circuit where the previous cell has died. So, just to visualize the situation is something like this say for example, you are in a network like this these are the individual neurons what I am drawing. So, say for example, this neuron dies out this one dies out and say this one dies out and this. So, now instead of them here you are putting some new neurons which you are assuming they will be you know they will form neurons some stem cells, but will they form the same connectivity or not is a big question. So, these are the challenges of the future will they become neuron will they press all the necessary ion channels to become neuron. We really do not know at this stage we are just speculating yes it may happen it will be helpful, but we really do not know or could we put a what certain you know electronic device out there which will get incorporated and re-established the connections. We really do not know these are some of the final frontiers where mankind is kind of you know or dreaming struggling and moving towards to understand who we are. So, at this stage after covering through the central nervous system peripheral nervous system briefly talking to you people over the last two classes about the memory learning sleep very briefly about the sleep and giving your overall picture I will close this part of the talk. And in the next class I will touch few smaller topics which I missed out in the course, which will make much more sense at the cellular level especially we in terms of the neurotransmitter excitatory inhibitory circuits. And that is where we will be closing down on the animal bioelectricity thanks a lot.