Okay. So let's go to the third possibility that we discussed. And this is the very controversial issue, whether newborn cells in the adult brain, often mammalians, like ourselves, exist. This is called a neurogenesis. Though you have new born cells. Is there a neurogenesis, in the mammalian, adult mammalian brain. We know that there is neurogenesis, that there are new born cells. For example, in song birds. We know that in some birds, in avians, there is a region in the brain whereby neurons are born in the adult male brain of the bird when there is a generation of the song. So each period this, the, the bird starts to re-sing its particular song for a given species, and, and this new song, new song, new singing of the bird is associated clearly with the addition of a large amount of new cells. This was neurogenesis in avians, in birds. asking whether there is a newborn system of cells in the mammalian brain. This was very controversial. Until very recently, we thought that there are, no, that you are born with a given amount of cell, at least for a given period of time Until you're mature and there are no newborn cells in our brain. Or in the mouse brain. So for example this was a big controversy eh, well known scientists from Yale said, not a single heavily labelled cell with the morphological characteristic of a neuron in any brain, of any adult animal. Any new, newborn cell and he concluded all neurons of the rhesus monkeys all neurons in teh rhesus monkeys are generated during prenatal and early postnatal life so early on there are newborn cells of course than there stabilized there are no indications of new born cells in that downgrade. But then in 1997 Elizabeth Gould a professor assistant professor of neuroscience in Princeton claimed she does see neurogenesis first in three shoes And later on also in monkeys. this start to be very controversial, but now today we have new techniques that enable us to mark specifically stem cells, newborn cells, in the adult brain of mouse and of human. And we know today That there are at least 2 regions, maybe more, at least 2 regions in the brain that constantly generate new born cells, new stem cells in the adult brain. This is one example of this staining technique. this is by Elizabeth Gould showing that these red cells are newborn cells and newborn cells following a challenging mouse water maze for the mouse and there are newborn cells in the hippocampus we mention hippocampus a learning region in the brain So this was indications of, because you have specific markers to newborn stems, you can see aha, our newborn stems. And now today for example at the Hebrew University of[UNKNOWN], using the 2-footed microscope and this staining technique, for newborn cells, stem cells. He's working on olfactory system. Not the hypo-campus but the olfactory system. He already, he showed the very beautiful experiment. That indeed in the olfactory system of the mouth there are newborn cells that are integrated in the system. Develop dendrites, become more extend, extended, making synopsis, making dendrites. Some of them die out, some of them remain, not very clear who is about to die out, the new ones, who remain as part of the system but clearly, the, a newborn cells in the adult mouse in the factory system and also in the hippocampus so this really changes the dogma the dogma that we don't have newborn cells. We don't have newborn cells is wrong there are two regions the Hippocampus also in our case ad the factory bar the factory system of the mouse there are newborn cells constantly being born, thousand of them every day. So what we know today -- so- -- sorry -- what we know today is that also human in the hippocampus generate newborn cells And these newborn cells are associated with a certain type of behavior or improvement of behavior, and apparently, and this is a very interesting case, where you challenge a mouse in this case with a very particular conditioning task, the mouse has to remember to respond to a tone if there was a tone here. He has to hold until presses the letter, for example, yes, and the task becomes more difficult with the gap between the sound and the reaction. He has to learn that he has to wait enough time. The more challenging the task is, so this is a challenging task, you have to wait a long time And this is less challenging task and, and so on. The more challenging task you have, the more newborn cells you develop. So there is a correlation between the birth of new cells. And we know actually today that these newborn cells are born as stem cells, in a particular niche Of the hippocampus, and they are migrated, they are migrated into a particular region of the hippocampus. And they become mature. They become involved. They become branched. They become part of the network, some of them. And some of them die out and this is an ongoing process. And those that remain apparently some of them are functioning, of course, for the network, and some of them remain alive, so to speak, for longer time, as a function of the challenges that the brain is facing. So there is the relationship between the number of newborn cells and the capability to to do new functions apparently that's not completely finalized this what I just said but it's clear that there is newborn cells some of them are integrated in the network in the adult mammal brain so that's a different than the old dogma now. One issue about these cells of course, and that's ongoing studies [UNKNOWN] in others who are they integrated with? What makes them stable or not? This is an ongoing research, because all what I'm telling you now is relatively new. One clear is that we would like to understand better, this phenomena of neurogenesis, because it provides hope for therapies. Suppose you have a region in the brain where cells deteriorate, dissolve. Can you rehabilitate? Can you improve brain capabilities, for example in Alzheimer's? Some how encouraging neurogenesis. There is neurogenesis but can we encourage more neurogenesis. Why in some regions like hippocampus we have neurogenesis, new born cells? In some region after a stroke you don't have neurogenesis. We would like to understand it, and this would be extremely important for. For disease, for, for im-, for, for ameliorating diseases. So I would like to summarize and say about this aspect of plastic brain. One thing is clear, the old notion of saying if you don't use it you lose it, is apparently correct. The more you use the network, a challenging environment, an intellectual task, motor activity, the more you challenge the network, the more new connections you have, more spines. The more new cells you have in the hippocampus then you have to learn something new. So the interaction between activity behavior and this plastic system that would like to change, so much would like to change, is about creating new spines and synapses, making the synapses more strong or weak. All newborn cells can really eventually influence your behavior. So you should be active, that's the message. So cognitive training programs can provide benefits. Physical benefits for the brain, for in health enhancement certain capabilities, that's a very important message for all of us. Let me complete This lecture, it is rather sparse but at least, I hope, giving you an indication of the status of the field, so to speak, today of memory and learning in the brain, about some anecdotes and questions that emerge from this study. Some anecdotes. Maybe many of you have heard About this classical FMRI, or MRI, experiment whereby you look at the brain of taxi drivers. And the finding was that these taxi drivers that are really in London and practicing to remember all these thousands, and tens of thousands of streets and stores and locations really high demand on the hippocampus of the taxi drivers in London. Apparently, there is a acorrelation between years of experience as a taxi driver learning the streets of London and, and, and the volume, and the gray matter volume in the hippocampus. This is somewhat controversial but, from what we just learn, is indeed the challenges of this hippocampus of the taxi drivers to remember so many streets and and, and so many addresses. Maybe there are newborn cells in the hippocampus that are stabilized. Enabling the taxi drivers in London to remember all these cells. There are other studies, many studies, actually, showing that when you are an expert in something, for example, if you are a musician; you very, very good in playing the violin or the piano, then certain regions of your brain, the motor cortex, the auditory cortex, region involved With this particular expertise. Increasing volume, whether this increasing volume results from most spines or for most[UNKNOWN] , not very clear. But there is this correlation and now I think you better understand what could be the underlying mechanism for this Non-invasive recording of brain regions that becomes bigger following, so, following for an experiment. So that's one aspect that I want to connect, because you may have heard this experiments. Now you know something about this cellular mechanism. Let me touch very fast about controversial issues. Or not controversial necessarily, but issues related to plasticity and learning. One aspect, and I already mentioned it, one of our amazing capabilities to change constantly. I know that after my talk, both my brain, and I hope your brain, have changed. You have new synapses or new spines, maybe even new cells Born after my talk, because you may remember some of it. But, so we are learning machines, but computers are typically not learning anything new. The computer, in terms of its hardware, its connectivity, its pattern of activity. So, there is a whole new field, a whole new field it called, it is called machine learning field in computer science. Whereby they are trying to develop algorithms and methods for he machine to learn and we are fantastic example of a machine that automatically built in in real time learning . Can we learn from the physics of the brain, how to develop sophisticated learning machines because if the machines will not learn they will never. Be even close to what we can do in real environment. So that's one issue I wanted to highlight. The machine learning field. Now we can ask yourself, how can you trust memories? You'll go to a trial, you'll go to a judge. You want to remember something. How can you trust your memory? [INAUDIBLE] not really I don't think that the role of memory is to embed forever a particular memory. The whole notion of memory is to try to assosciate and change constantly while you experience new thing to associate now what you've learned to something that you've learned before So memory has to be versatile, has to be flexible. And this flexibility may really harm, so to speak, a given memory. And there are beautiful new ex-and experiments showing, that when you use the memory now, when you bring out the memory now. The fact that you now bring it out with the new association, because it's not the old memory, but now it's a, the memory in a new environment already changed the memory. So it's not a fixed thing, the memory. We should not look at it as a picture that's in the camera that remains the same picture. Or in the computer the same, the same word file remains the same word file, no. The memories are very flexible that enables[INAUDIBLE] mechanism enables us to interact with the world, and change our perception of things on going. It's not a trustworthy reliable forever. Could we read out memories? Could they look a your mind and say now you remember you mother, now you remember your childhood. Can i do it? The general answer is no because you code the particular memory with a given network that is particular to you. You code the color red differently than I code the color red. We then agree that when we look at something, it's red for you, it's red for me. But the coding, the spikes, the synapses, the particular neurons involved in, in your red, in your association of red with a rose. My association of red with maybe blond is different. So I cannot just look at your brain now and say now you think about red. If I look at your brain enough times and I decode your particular brain, I develop a polygraph for your particular brain, then I may be able to read something About your particular encoding or coding of a particular item. So it's not going to be disc on key because we don't have a common disc. You have your own brain and discs. And I have my own brain and discs. We cannot exchange easily discs. Language helps to exchange discs. And finally, I want to ask could we embed new memories? Can I stimulate your brain and embed new memory? Of course I can do it. I can embed new memory now that I teach you. So I embed new memory in your brain. I can stimulate your brain. I can erase memories. I can destroy synapses, I can intervene with your brain. That's true. But I cannot really, in particular, embed a face, because I really don't know how to really manipulate your network so whenever this network is active, it is associated with a given item. I have to correlate the item with a network. So I have to stimulate it and then show you something. Stimulate the network, show you something. Then you do the correlation, you do the association. I cannot really embed a face, unlike many movies. So our brain is very unique, very particular, and it requires a very, very specific network to be active Associated with something on the outside. Then you make the association, then the memory is embedded. And as I mentioned earlier, you have also to act, you have to behave if you want to perceive, like in the case of the twin case. So, thank you very much for listening to this lesson number 5. This was an attempt to integrate data from anatomy, synaptic physiology, spikes, and new experiments about the brain related to a fascinating phenomena, memory. In the next lesson, we should talk about another aspect of the brain, computation. we are a computing machine And I want to show you how neurons, dendrites, synapses and spikes can compute, can be used for computation. So see you next week.
