Okay so welcome to lesson number seven today. Last time we discussed in relative depth modeling in neuroscience, theoretical neuroscience, computational neuroscience. In particular, single cell computation. And today I want to go into the blue brain project, the human brain project. They call this lesson number seven cortical networks, which we should focus on cortical networks, discuss the cortics before. But in particular, I want to call it out of the blue project, which is of course again between blue and out of the blue. And we should try to understand. What do we do? What is the aim, what is the purpose of this project? So I will start with a description of several mega projects. So the blue brain project is only part of several of them that are now ongoing. Just to highlight a few of them. Then I will discuss the cortex very briefly just to give you an introduction to the cortex, and in particular to the cortical column. The notion of a column in the cortex, and then I will show you that the column, the cortical column, is used, or was used now, we are going further but was used as a test case, as a proof of principle whereby we want to see whether we can take whatever we know about this column of the cortex. Can we simulate aspects of it, and then eventually I want to describe the human brain project which is much beyond the blue brain project. And I would like very much to be able to emphasize the difference between the blue brain project, which was the test case, and the human brain project, which we just started. So I promised you a perspective on several large, mega projects. When I say mega, I mean this is really a lot of investment, huge summations, billion of dollars, billion of euros. So it shows just four. I could choose a little bit more. So one of them is the Allen Institute, Allen Institute in Seattle. A very interesting place, a very interesting concept by Paul Allen, who developed this institute which is growing very nicely, very fast. They already, in a sense completed the first mission which became very useful for neuroscience, what they call the mouse and the human brain atlas. Whereby the develop methods and also analyzed the expression of genes, different type of genes in the brain of the mouse. And now they are doing the same on the human brain. Which is, as I said, a very important endeavor because we would like to know what genes are being expressed in the mouse, in the healthy mouse brain or in the sick mouse brain. Whereby, hopefully we can better understand interactions between certain diseases and certain genes. But, now, recently, they started a new project, there, in Allen Institute, focusing on the mouse visual system and one may wonder why the mouse visual system. The mouse is not the best seeing animal but still they decided after a big debate on what should be the next project. They decided on the mouse vision system and part of the reason is that we know a lot about the mouse visual system, both anatomically physiologically, and also one can develop many many new tools, genetic, optical tools to study the mouse visual system, or any other system of the mouse. And so the mouse is a very good experimental system for understanding the whole system, in this case the mouse visual system. So Allen Institute in Seattle is a very prominent, very promising, very successful institute for brain research. The next one i s Janelia farm, not far from Washington D.C. and they are supported by the Howard Hughes Medical Institute. They developed really an industrial scale new institute, very impressive also architecturally. And there they develop methods and also a very fascinating experiments to study the interaction between anatomy of particular systems. Mouse, sea elements and other lower level, so to speak, animals to connect anatomy and physiology to specific behavior of subsystems. And this is really extremely modernistic, I should say futuristic center both technologically also aesthetically and also conceptually how to go about studying particular systems. Very expensive, very successful, very new. I highly recommend to visit there just to see how modern science is being performed. I will talk a lot today, of course, about the human brain project because I am involved in it, and it came out from the seed of the blue brain. I just want to now just say that is located in the center at of the EPFL, it's a whole European project. But the focus the center is in EPFL in Lausanne, Switzerland. The idea is to develop new platform, not new experiment, but new platform to study the brain, new way to integrate data, to integrate knowledge from different disciplines, both physiology, and anatomy, and computation and engineering and other technologies I will mention later on. And hoping that this integration of data under one umbrella, under one platform will enable to really enhance, accelerate our understanding of the brain. Both in disease, And enhance and eventually, the hope is of course, to try to develop new treatments from brain diseases due to this encompassing, this integration new platform that we propose. And recently, I already mention it in the first talk, I mention it a little bit more today. Although I'm not going to discuss it, of course, and it's only starting so it's ongoing debate what exactly is the President Obama Brain Activity Map, or BAM, Brain Activity Map project, or initiative. But the general idea is to develop new techniques. To measure the activity at the single cell level. The activity, the spiking activity at the single cell level, for millions or maybe even billions neurons simultaneously in the living, behaving brain. So that's the big mission of the brain activity map of President Obama, which is very debatable, as all such a big projects are always debatable. I will mention later on, but you already studied a depth, the Hodgkin-Huxley model and what spikes mean, the spike mean. And so the brain activity map is to record many spikes in the behaving brain, hoping that when you see a brain active at the level of single cells, you may be able to understand certain aspects of coding, decoding information, representing information, and also what happens in the diseased brain. So that's the idea behind the concept of recording for many cells. We cannot do it today in the behaving cells at the level of millions or billions. We can record from hundreds of cells or maybe thousands of cells, but certainly not at this level and that's the mission of the BAM project. This was just a survey and they already mentioned diseases. You may know that one of the aspects of brain research, and not the focus of all brain research, is the aspect of diseases in the brain. Unfortunately, and I mentioned it in the first talk, unfortunately this very delicate, very fragile system generate diseases of many, many types. Here, all the names of known neurological or neuropsychiatric diseases under a project called the diseasome. An attempt to systematically, based on what we know about genes of certain diseases of Parkinson, and Alzheimer's, and schizophrenia. And depression and all this many, many, many diseases that we know today. What is the common ground, what is the foundation? Genetic foundation and other correlation between different diseases, so this is an attempt to systematically some how put all the disease under one frame of, and this is also part of the big attempt worldwide to make sense, so to speak, of diseases. This is also part of the Human Brain Project, which I will mention later on. So disease, of course, is a big drive for all these big projects. Humanity needs to solve the problem of the brain. I mentioned some solutions that are more symptomatic. Would like to understand the depth, the deeper aspects of diseases in general. So we know all these diseases emerge typically at older age, but not always at older age. For example autism is not a disease of an older age, but Parkinson maybe yes, and Alzheimer's certainly. So, we need to understand how diseases and in particular, and that's the point that I want to emphasize and we already did, that all these diseases, all brain diseases emerge from some aspect of activity or anatomy, or both. Some misbehaving region, in some sense or a connection. All the excitability, spiking activity are both in a particular set of networks. Something goes wrong. In many locations, together the system generates a behavior, an output. That is not the appropriate one and disease comes up. Whatever disease means, our definition of disease and so forth. And I already mentioned before, I think in the first talk, I already mentioned the work of Professor Hagai Bergman from our institute, from the university. Who is working on a particular region of the brain. I already showed you an activity of a so to speak normal non-Parkinsonian piece of the brain. In this case it's not the cortex. We caught it not from the cortex but from deeper brain regions. The massive ganglia but the principal holds for any region. You see an activity that you call normal, that is not associated with Parkinson in this case. And then you'll see it, the activity, electrical activity, spiking activity and now you know that each one of these bleeps, each one of these signals is called a spike, so you can see a spiking activity of three cells in this case. Recall that simultaneously, whereby you see that the change in activity is associated with the disease. So we want to understand what is the mechanism, what could be the mechanism in this particular network that generates a wrong electrical activity underlying Parkinsons. So that's one of the big mission of many of these project including the Human Brain Project. Not only describing the disease electrically but understanding the underlying, the underpinning mechanisms. Synoptic Electrical activity combination of them and so forth that gives rise to this and not to this. Hoping that by understanding this, we will better understand the disease.
