 Welcome back to the lecture series in bioelectricity. So we are into lecture number 22, in the previous lecture we talked about summarized all the different sense organs like vision, hearing, taste, alfaction, touch, pressure sensors all these things. So at the high centers of the brain all these informations are coded, electrical signals are being coded at different regions and we remember all these informations they get consolidated over a period of time and this consolidation of these informations which we recollect whenever we needed is called memory which is one of the central problem in science how biological systems remember things. Whenever we think about memory we think about you know in electronics we talk about binary codes 0 1 0 0 1 0 1 likewise and these binary codes code the informations on CD disk or in mobile drives and so many other information storage systems. But how does biology do so? How does electrical impulses remain embedded within our system in what form? How they retain throughout their life? How we recollect things? What happens when we sleep? Why it is being saved that suppose you have an exam tomorrow morning so you should sleep tonight you should not do a night out because then your mind will go blank. Most of these questions are the questions of the or the questions which will take us to the next frontier these are pretty much the final frontier who are we and what is that thing which ensures our very core of our existence. Because these questions we even becomes more profoundly challenging when we see Alzheimer's disease patient a patient who loses his own identity they forget who they are they forget the whole surrounding because there are certain group of neurons within the brain which starts to die for totally unknown reason of course it is known that they form certain aggregated moieties a beta and bunch of it but why it is triggered is not known. Similarly there are patients of Parkinson they lose all their motor functions there are specific areas within the brain which starts to die out yet there are patients in whose situation the motor neuron in the spinal cord starts to die out they suffer from amyotropic lateral sclerosis. So all of them have one common feature wherever these neurons are dying out the assigned functionality of the neurons of that area is lost and if it is lost in the hippocampal region and the surrounding cortical region it is termed as Alzheimer's disease where the person completely suffer from a permanent dementia they forget everything and in and around and they die without really knowing who they are it is very sad but that is the harsh reality of life that who are we is also fairly we do not know. So this subject for centuries have inspired the psychologist scientist and in the modern world the neuroscientist people who work on consciousness memory so on and so forth today we will just study kind of scratch on the iceberg because there is a huge amount of literature on all these things they are pretty much subject in themselves but what we will be doing will be talking about the anatomical features of the brain and the electrical signals which are believed to code for memory acquisition and memory storage machine a very little of it and of course we will be talking a little bit about sleep and different rhythms of the brain and the tools used to understand most of the brain waves electroencephalogram and the different kind of waves which are found in the brain. So before we embark into this brief journey to the very deep recess of our brain which distinguishes who we are we need to assimilate all the sensory informations what we have gathered by assigning the part of the brains where they are getting stored. So first thing we will do I will draw the brain overall anatomy of the brain and we will locate the different spots in the cortex or in the cortical region where the different informations are being stored. So to start off with so this is lecture 22 so here we will be talking about memory learning electroencephalogram I may not follow the same sequence but I am just kind of enumerating Alzheimer's disease Parkinson's disease and of course we will be talking about the brain anatomy very very briefly though brain anatomy and different cortical regions may be talking about memory and the different models of memory the existing models learning sleep such a brain waves sorry brain waves and EEG which is also called electroencephalogram we will be talking about sleep talking about Alzheimer's disease Parkinson's disease a little bit of we will be talking about ALS or amyotropic lateral sclerosis and some of the prosthesis to start off with so we may need to you know move on to the next class to cover some of these topics but to start off with let us talk about the different regions of the brain which store different kind of information so in the next slide let me draw the overall architecture of the brain so if you look from the top the brain pretty much looks like this so there are two halves of the brain and they are connected by a tissue which is called corpus callosum corpus callosum okay then you have here the prefrontal cortex prefrontal cortex then you have speech area then you have writing area then you have auditory cortex of right here auditory cortex of right here then you have some area out here which is called general inter creative center or mostly language and mathematical calculations and out here you have the visual cortex for right eye okay and then you have now on the other side if you look at it you have the sense of touch then of course you have the auditory cortex the counterpart on this AC then you have spatial visualization and analysis which is sitting somewhere here people there are certain people who could you know imagine three dimensional structure far better than other spatial visualization and analysis and likewise in the fourth so this is the right hemisphere and and this is the left hemisphere and it has been observed that this is the right hand and the as is I have already mentioned the right eye the information is processed on this side and the left eye the information is processed in the opposite side this is the left hand likewise okay so if you look at it what is very interesting to notice these different areas so this is you are seeing from the top so if you look underneath if I just go a little bit more on the anatomy and if I have a side view of the brain it will be something like this out here you have organ called pituitary which is the neuroendocrine organ here you have the spinal cord see and out here deep inside there is an organ called hippocampus the seat for memory the name it got the name because this organ is in Greek it is called seahorse and since it almost looks like if you kind of you know get a get a three dimensional view it almost looks like looks like a seahorse and that is why it got a name you see a seahorse the first question is how it was discovered that it is this organ which is the seat of memory so all these started somewhere middle of last century around 1930s and 40s before that this whole area of memory acquisition and memory was clearly dominated by the psychologist the modern neuroscience has its beginning from the time of Ramon Y. Kahal in the very early 19th century 1901 1910 Kahal made his seminal contribution where he did it silver staining with Golgi you know silver staining and all those things and the whole anatomy was fairly clear and it was the same time when Sherrington and all other people slowly electrical responses for the neurons were being started people have started recording all these things so that was the kind of beginning of what you see today's modern bioelectrical phenomena of the nervous system somewhere around that time so 1940s there was a very unusual event so and simultaneously there was another group of thinkers who are developing learning models so one of the learning model which was developed during that time was developed by a guy called Donal D. Hebb which is also popularly called Hebbian and this is he was psychologist Hebbian learning model the very interesting model this is among the very in the present condition of most primitive or the most or the first one first of the learning models which essentially say it very interesting thing it says say for example there is a signal generated by a and there is a receiver of signal B a is the sender of signal and B is receiving the signal and both of them are active at the same point of time then and this information is getting so I am just putting info info info is transmitted from A to B it may happen after a point even when a stopped sending signal to B in other word there is no more signal going from A B will still keep on receiving signal from A sounds to your very paradoxical situation because A is not sending in sending in a signal after a point but B is a still active as if it is still receiving signal and it is being said it is that at this stage this is the stage of B when it store information but this model of learning and this is where the permanent changes takes place in the network properties lead to the acquisition of information at this stage but this Hebbian learning or Donal E. Hebb's learning model was not proved in biology till 1970s or half way through 1960s but in between something else happen. So, if we talk about the Genesis of Hebb's model it was around say you know nineteen I would say nineteen thirties and nineteen forties this learning model was proposed this is a theoretical model nineteen forties late forties accounted for a very interesting piece of event which took place in one of the hospitals in Canada what happened exactly there was a mine worker this mine worker had a pathological problem he was he was he was suffering from chronic epilepsy. So, very frequently he had to you know he is to get this epileptic bouts. So, what essentially happens in epilepsy is something like this say for example, if this is your brain and this is the spinal cord and you know these are the different organs and I can know I is here and likewise. So, the epilepsy bout all of a sudden this whole brain this whole thing becomes hyper excitable hyper excited this is once again he p ellipsic and when it become hyper excited. So, there is pretty much collision of informations and this person lose pretty much coordination with rest of its system like all this peripheral system and this system they kind of disaligned from each other there is hardly any control left and this person faints and these kind of epileptic bouts could be very dangerous suppose you are driving or something like you know you lose complete contact with your peripheral system. So, this mine worker was suffering from chronic epilepsy problem and every now and then he had to take a leave and he had to go through the medication and everything. On one occasions the neurosurgeons did something very interesting what they did it was they could figure out the zone of the brain from where this you know hyper excitability is originated and it was observed that within the brain again I am I am just going by the side view of the brain if you look at the brain like this and this is a side view this is the spinal cord medulla oblongata and these are the different cortical regions what I have showed in the first slide. So, out here I was highlighting about the area of hippocampus. So, what the doctors did was they surgically remove this part when they remove this hippocampus from the brain of this mine worker this individual got rid of his epilepsy though did not suffer from epilepsy, but from that day he never acquired any further memory. So, he lived like you know what is over the stored he never from that day he never remembered anything is not that very strange, but that is what it is that is what happened they remove it. So, the result so you are removing it I am just showing a minus sign no further memory acquisition. So, this person lived all on his previous pieces of information never learned anything after that this experiment or this is a real life situation you can call it an experiment or this surgery by the doctors during nineteen between nineteen forties and nineteen fifties open up the question of learning and memory again in a much more bigger way, because now the doctors realize or the neuroscientists realize the major organ or one of the if not the major, but one of the rate limiting organ in memory acquisition or memory storage or information processing apart from the cortical regions is hippocampus. So, if you look at the historically this was an absolute accident, because doctors wanted to help this patient and I know they just removed that part of the brain which they were suspecting that is from where most of the epileptic bouts were originating. And result definitely minus one of the epilepsy, but minus minus minus no further memory acquisition, but now the question arises is this area could also show what has been proposed by Donald had fairly on the same time does this area showed any form of heavy and learning model and if so how is it. So next thing came, so I am just highlighting those wonderful work which had been done by a bunch of people during the last century which set the tone for our modern day research in understanding the memory acquisition phenomena. The next thing came was done by three gentlemen, Bliss, Lomo and Colin Gritch. Bliss, TVP Bliss, Lomo and Colin Gritch and the venue this time was Europe, so this happened in Canada and now back in England. What was being done is that in again a pick they remove the second let me draw it they remove the hippocampal region. So now you have a wonderful hippocampal tissue out there and in that hippocampal tissue they implanted electrodes like this. I am just putting the electrodes now and by the way this hippocampal structure is very well organized it has different regions which are named as C A 1, C A 2, C A 3 and underneath there is a region called denturgiars. So they implanted electrodes out there multiple electrodes and they implanted electrode in another anatomically another distinct region of the brain within the hippocampus. So let us name these electrodes as irrefutable region A and region B and what they did they started giving stimulus from here high trained stimulus going. So automatically through this pathway so this is a connecting pathway the signal will be reaching here. So on these electrodes you could now receive the signal. So they are receiving signal now say for example up to time say T 1 to say T 15 I am just taking arbitrary numbers time 1 to time 15 they kept on giving stimulus and automatically as they were giving stimulus electrode B was receiving the signal. What they did at T 16 on they stopped giving signal and what they observed was B is continuously receiving signal in spite of the fact T 16 on for a while for a fairly good amount of time in spite of the fact there is no more signal coming from T from the ADGN. This was a stunning discovery so it means now if you go back to the Hebbian learning model A is sending signal B is receiving signal but after a point A stopped giving signal stop no more signal is still B is receiving signal for the first time this was a wonderful journal of physiology paper for the first time Hebbian learning model was proved that indeed there are regions in the brain which follows a different set of computation and this process of memory acquisition was termed as long term potentiation which is one of the most accepted models of memory acquisition which in the short is also called LTP. Now the question arises sure this electrical phenomena does exist but does this phenomena exist in the intact brain or not because this is a slice of tissue which you have taken out this answer in last 50 years we have not been able to answer this still we have a long way to go but this question has just opened up the whole field of neuronal computation electrical signal processing that what exactly is happening so now the first question which comes in mind is that between A and B is it if I consider these as presynaptic and the one which are sending signal and these are post synaptic neurons then is this a presynaptic phenomena or is it a post synaptic phenomena and if it is what is over the phenomena is are there retrograde transport available are there messengers which are sent even after the signal is over are there signals which are being sent to A telling that you keep on sending more and more signal in spite of the fact the external signals have all stopped there is no more external signal being given if these are considered as external signals then if is it it is so which is suspected it is so then what are those retrograde messengers who are those retrograde messengers there are indication towards very simple molecules like you know nitric oxide you know arachidonic acid glycine likewise but again none of them have been proved beyond doubt that yes these are the retrograde messengers still there is a lot of controversy over the fact that is it a presynaptic event or is it a post synaptic event what we know for sure is this phenomena indeed happen heavy and learning model indeed work but this happens when there is a very strong train of signals sent by A strong train of signals now the question arises what are the permanent changes which are taking place in the post synaptic membrane permanent changes in post synaptic membrane these are the questions which people are trying to address but there is another thing which comes in mind so this is a situation when say for example you are trying to remember a new poem or a new piece of information intense on it okay two on the two to two the four to three the six or something like that but say for example you just observe something for a fraction of a moment or you see a snake or you see a blast you still remember it so in this situation the signal is not very like you know not a huge train coming for a while is one spot moment is does this follow as follows a long term potential model or say for example you do bicycling you are biking you are walking how these are coordinated you never do a memory recall that all these processes there must be other coding information and that takes us to the next set of information coding which falls under another model which is called long term depression model will come to that but before I come to the long term depression model what essentially is happening so when if we believe now the way the current theory says is if I am giving a side view of the brain now out here if this is the area which is involved in the hippocampal region so it is believe what is happening is this first of all the sensory inputs are reaching here through the spinal cord the OLO are showing the sensory inputs okay all these different sensory inputs these sensory inputs are initially stored just like a buffer memory out here just what you see in a computer as the RAM random access memory buffer memory or you can call it random access memory RAM chip okay the bigger the RAM you have better off you are then from here there is a consolidation phenomena takes place where basically the information are sorted out if you remember when I was telling you that if you go back to the first slide second sorry yeah this slide so they are different region the speech component there is a writing component there is auditory component there is a special visualization component there is a touch component there is a visual component visual cortex out here likewise now coming back to this it is exactly the same thing now each one of these different components are going to their different regions if for example we observe something we observe and say you know an apple so it has see look at the component it has a color it has a taste it has a texture it has a shape maybe it has some emotional value with your something you know so all these information so for our nervous system these are electrical signals these different electrical signals are stored at say color region taste region texture region shape region likewise so the same thing is coded at different places and whenever we have to recollect this all has to be further integrated to realize that this is an apple so essentially what is happening is your hippocampus is acting as the zone of buffer memory and from the hippocampus slowly and gradually the information are being transmitted to the different areas of the brain where they are permanently stored so when this zone this area is started to die off we do not acquire any further memory and many a times we lose our own identity what exactly happens in the hippocampal region of course will come in depth about the cellular architecture of this and the information so before I even go to the long term depression and all other models this is very interesting to understand that you know how this area actually so as of now this is the most accepted model of memory acquisition that something happens or some memory is acquired in the hippocampal region and it is being slowly you know transmitted back to the different regions of the brain where different pieces of information are getting stored in the bits and pieces okay so what essentially happens in Alzheimer's I am not entering into the long term depression at this stage I will be getting there very soon so what happens in Alzheimer's now first of all we have to look into this structure so let us investigate this structure this structure is I told you is a structure like this so this is structure is a multi-layer structure it is a very three-dimensional structure this is not something the way I am drawing it is much more complex structure like this okay so now here the neurons are at different level neurons are kind of you know layers of neurons which are present out here and most of these neurons have a very characteristic shape their cell body is more like a pyramid and these are called pyramidal neurons pyramidal neurons and during Alzheimer's what happens is that out here there is a accumulation of there is an aggregation of certain specific proteins which are called a beta proteins and which the current if the current theory has to be believed leads to a blockage in the electron electric ionic electricity transport pathway and eventually what happened their cell bodies their processes the start is to die out what I am showing now the process started to die out and these cells failed to communicate with the rest of the system because their processes are now being chopped off by this a beta peptide which is getting accumulated and the electrical signal does not pass through and eventually this whole part of the brain you go back and see the side view of the brain this whole part is kind of you know gone all the pyramidal neurons dies out here and that is what leads to an Alzheimer patient to lose his own identity same way they are a region within the brain like if I go back here but here they are within the cortex there are motor cortex areas of the brain where there are motor activities which are involved the areas of motor cortex within the motor cortex there are very specific areas which are called substantial nigra just highlighted in the motor cortex there is this area called substantial nigra these this area there are motor neurons which secretes dopamine and this is dopamine secreting motor neuron and it is this area which coordinate motion now for some absolutely unknown reason this substantial nigra motor neurons started to die out and what happens this motion coordination is all lost and this is the disease which is called Parkinson disease so if you look at if you compare the previous slide where we talk about Alzheimer's disease and this slide if you are comparing it with the Parkinson disease both of them are neurodegenerative disorders where the neurons are getting degenerated but there is a fundamental difference between the two the fundamental difference is that in the case of Parkinson disease you are losing your motor coordination and in the case of Alzheimer's you are losing your very basic who you are you cannot acquire any further memory but a Parkinson's patient does not suffer from dementia so though this process of neuron death is fairly similar in this case alpha sinically and there is a protein which is getting aggregated out there in Parkinson's so they all if I if one has to give they all fall under a protein aggregation problem somewhere or other then machinery through which the electrical impulses are being transmitted are getting chalked up or blocked or as if there is a traffic jam out there so if you really look at these neurons the way they they are like you know if I have to show you in three dimensional picture so there will be something like this what what you kind of inexperiences these are the process all over the neurons you know this is a body so what you see there is a lot of aggregation of proteins out out here and because of this aggregation the electrical impulses which are originated out here fails to travel through this and eventually they die out so this is the protein and peptide aggregation so both Alzheimer's and Parkinson's and even a myotropic lateral sclerosis are fairly similar problem there is a neuro degeneration but there are different proteins involved and it is very interesting that one area does not influence as the other areas of now with their own knowledge but end of the day that destroying that part so now if you see this image what I was trying to show any of these area if any of these area kind of you know is affected by any specific disease then we will be losing that modality or say for example is there is a problem in the visual cortex we lose vision if there is an auditory cortex problem we lose the auditory ability if there is a problem in the writing cortex we lose the writing ability if there is a problem in the touch context touch cortical region involved in touch we lose the sensation of touch if this region is kind of getting affected the spatial and visualization analysis then we will be will not be able to coordinate and if there is a damage in the corpus callosum then the connectivity and crosstalk between the left and the right side of the brain will be hampered so this is what I wanted to highlight in terms of the long term potentiation and the memory acquisition process so what will we do I will close this class here in the next class will be talking about long term depression and we will talk about all the brain waves which are involved in it and little bit about the sleep okay and then we will talk about some of the neuronal computation and neurotransmitters thanks a lot.