 Nearest scientist And he's going to talk about optogenetics, so Okay So thanks for the election in Guinea So hi everybody. So my name is again. He is here already. I'm your scientist from Martin Street from the bicentrum. I love you there and Today I'm going to talk about optogenetics so pretty exciting Pretty exciting topic so for many neuroscientists, and I think that I hope that by the end of my talk you will kind of share this feeling as well So that is not my talk with a bit in a weird way So I want to tell you first what optogenetics is not so optogenetics is not optical genetics First of all because it's not second because there is no such thing as optical genetics, you know So just avoid any confusion from the very first slide and before we come to optogenetics So let's jump back to the past to 1997 So those of you who are approximately of my age might remember this movie So and maybe you also remember who were these two guys and what they did with small device here their hands So this device is just a bright flash light What they did today they try to erase memory of other people so that they don't remember at all that they have ever met these two guys Yeah, because there were secret engines logically So pretty brilliant idea For that kind of movies science fiction movie with 1997 now we have 2017 right so and I think you wonder how much you have advanced in that time over the last 20 years in this technique And we control brain is light and I'm happy to say that we do we can't control so since 2005 at least Unfortunately, I have to admit we can't control that only in animals so far and also with this nice idea with this flash light Also didn't work well so that we have to deliver light directly to the brain using optical fibers So in blinding on the animal head, so here we come to the point So what is up to genetics of the genetics so we can say that it's a way to control brain is light But given that the goal of science in general is not to control brain of mice So therefore I was rephrased in the way of the genetics is a tool to study brain to study the brain using light and thumb genetic engineering so Before we before I explain you what that's how it works. So Let's watch the videos which will demonstrate you how much we can influence animal behavior Just by flashing light particular areas in the brain. So the first video, you will see a mouse here Optical fibers and found it to deliver light while this optical fibers to particular brain region Which is controlling aggression and hunting behavior in mice. So mouse will run in this transparent plastic cage and Beside the mouse, there will be this object here just wouldn't stick. So which is unfamiliar to the animal animal have never experienced that So what happens usually animals just try to find out what it is. They just run around check smell touch This post touch with the whiskers. So to kind of check how dangerous the option is And then this corner here, which is we'll see the status of the light source that we use in this case It's either on or off. So let's see what happens. So when we switch the light on So, okay exploration. It's kind of slow down the speed of Just piece of this space for exploration now. So let's see what happens the third was on And animal suddenly changes behavior and start to attack the object Trying to buy this trying to destroy it. It's totally unusual behavior this case. So they never do this At least before they learn the object Okay, that's fun. It's normal. Let's go to the second one. Yeah, we have similar situation animal in the cage So optional fiber illuminating different brain region, which is responsible for feeding the cells to you or for drinking behavior And this metal tube here is just tip of the bottle So this water and the main point here is that animal have absolutely free access to water all the time So there is no any restriction distance So Let's see Again, just breaks the relation of running around smelling around everything as usual now light is on and immediately after that animal starts drinking and it keeps drinking and drinking and drinking while the light is on and just stops When the light goes off and if it is multiple times animals will just drink multiple times So as long as the light is gone So I hope that kind of these two videos Made you a bit curious. So how this technique works in general Of course, if you just speak random animal and light and illuminated with a light I don't know from your table lamp. It will not work So you kind of have to do few manipulations with the animal and use special light So we will talk about this but before we talk about that. So let me give you few Just remind you a few things about brain functions so you can understand what I'm talking about So brain is a very complex structure that we all know So brain consists of multiple regions each region has own function and each region also in turn can consist of multiple Neurons of different types. There are multiple types of neurons a different day shape activity level composition and so on so on This neurons are interconnected with each other and constantly interact with each other One of the main features which differ neurons from other cells in the body is that they can generate electrical pulses which Spread along the bodies from one end to another end So it means that when I say that the neuron is active or the neuron is Activated by something so I mean that the neuron Generate an electrical pulse either single pulse or a series of pulses doesn't matter and If you have pure neurons connected to each other But such a pulse reach the end it can activate the next neuron that you will activate the next neuron next neighbor And so on and we can say that neurons can interact with each other by means of this So which mean that when we say that we can control brain We mean just that we can control neurons in the brain and Controlling neurons just means that we can force them to generate this electrical pulse is when we need that independent from the spontaneous activity and any processes which Happens within the neurons so that we can know now. So what I mean when I say that we can control neurons Good. So now let's come Let's come to the So let's start from the beginning When we how it has been invented As usual this high-tech idea came or was adopted from nature namely from pretty Simple species holds real algae calamity of waters like you can see that this algae algae algae You can figure you can find basically in any pool outside, especially in the pool is not clean properly So it's just single cell organism. They leave usually close to the water surface because I need light for photosynthesis The interesting thing about this organism is that it has special light sensitive organ inside So which helps them to orient towards light and moved towards light This organ like the poor element of this organ is like that the protein called channel of obscene At this point, let me just give you like small command like small side command So this just for the next slide. We don't need that. So this protein is present in this Organ organism just because this organ has a special gene Which was this protein so it means that the organ is can produce the protein on its own using this gene So just keep it in mind. You need it next slide. Let's come back to the channel obscene channel obscene is a light-sensitive protein It means that it responds to blue light By letting positively charged ions to go go through the membrane into the cell You can think about it just as a about simple channel or just gate Which is close to the normal conditions without light so that no positive ions can go through When you shine light it opens and the positive ions go into the cell If that's exactly what neurons need to generate electrical pulses when many positive ions go through the membrane to neurons They generate pulses So therefore no wonder that scientists come up with a fresh idea. They said okay. So neurons usually Have no channel obscene. They're not sensitive to light What happens if you take channel obscene and insure that the official either to neurons traditionally is Can you make neurons sensitive responsive to light by inserting this protein to them? So we can illustrate it by this diagram here. So we have channel obscene insured it To some neurons, let's say it was selected you was because you don't want to activate for brain. We just want to activate specific group Then we shine light What happens then so in neurons, which have channel obscene this channel get open positive ions go into neurons and neurons generate their own pulses or That's why it feels So either they start generating pulses or they just generate more pulses and they would have done so under normal conditions Right or then compared to other neurons which do not have channel obscene So the idea has worked out in 2005 Toward this goal scientists had to basically solve two technical problems Problem one how to insert channel obscene to neurons problem two how to do a light to neurons Let's just go one by one So first problem how to insert here. We need technique which is described by the Second half of the name of the genetics. We need some genetic engineering. So what can we do here? So we take with it again extract Gene of channel obscene. So here I just want to stress that We don't take the protein. So we take the gene which was approaching because the only way to insert this protein to neuron In the way that it stays there long enough like few months at least So it's inserting the gene inside of the protein. So to make neuron making producing this proton on its own Right. So we insert gene How to insert gene to neurons we use why they use technique here Which is now very popular in science. We use virus as a transporter insert gene to that virus and We inject virus to the animal brain To specific area, which you want to activate later So what happens then so this vital particles attached to neurons inject genes to that neurons and these neurons start producing Channel obscene for the soul. So it looks like you can see here. So some neurons Inactive neurons have channel obscene and they become light sensitive The last question that we have to fix now is how to make it neuron specific. So it will not own all neurons Express channel obscene So I have no time to go into details here. Please. Just believe me. There are techniques in genetics. So let's call them genetic tricks So using the genetic tricks we can insert channel obscene to particular neurons on there so Next question the next problem that has to be solved is how to deliver light and Here we deal with the first part of the day of the genetics optics, right? So of course we need light source and Channel obscene is sensitive only to blue light. So it means that we need a light of particular wavelengths So therefore we use in the laters or powerful light meeting diet So that's and to deliver the light from the source to the brain We just use classical optical fibers nothing special here. I'd like to see sorry like you see here and Because it's color the animal is not transparent for light and fortunately We have to research it we have to make small opening in the skull like you see here that the skull and Here it's more opening and we have to ensure the Optical fiber to the brain and then we fix everything in the In practice, of course, we don't insert directly the optical fiber But rather we insert the implant special adapter so that we can plug it and plug the fiber So when we don't do experiments animals, we don't we don't connect And then eventually what we get we get the animal which is genetically modified animal So some neurons in this animal in particular area express channel obscene and they become sensitive to light And we have way to deliver light to those neurons. Let's see what happens within the brain of this guy, which so again, so they have Neurons some of them have channel obscene. They're sensitive And in all conditions and we don't eliminate with light so they have just normal activity As soon as we switch light on Here they must be light, so I don't know why I don't see it But anyway, we have light here. So those neurons become active and generate the electrical passes, right? And the main point here is that only those neurons are activated while all other neurons which have no channel obscene just stay Not affected at all. So they just stayed up in the same activity level as before And that basically how the genetics works because now as soon as you have a subset of humans that you can Control is light. You can test your hypothesis. You can test whether they important for that function for that function You can activate them and also we cannot suppress them. I don't mention here, but there is a way to suppress them so Coming to the end let's Overview kind of what kind of application we can do with this technique First of all, let's talk about science because in science optogenetics is applied since 2005 The main breakthrough that the genetics was brought to the science is that we can control Braille activity at a level of individual neurons or small group of neurons And that allowed scientists to identify small brains So it's small brains like small neuron groups, which are responsible for controlling and equal physiological functions So I can illustrate it with this picture here. So let's say that our initial stop stopping point you could say That this brain region is huge cortical cortical vision here is responsible Let's say for just arbitrary decision-making That brain region was critical for memory and what we have now is more or less like this So we go into details in please resolution and we can already identify very small circuits within the brain Which controls different functions? And also it looks like if you want to imagine that think about images of the earth surface done by satellites, let's say four years ago when they would see Only big cities on the images and now you can identify individual persons in the street So that's kind of gives you an estimate of the change that we have now without genetics Good. So the second research direction Which really benefited from genetics is the discovery of new Treatments for neurological disorders using animal models What I mean here is following if you take animals and genetically modified them to simulate a particular human disorder And you say no, which neurons are responsible or which neurons do not work properly? And that's a reason for particular symptoms of that disease You can restore their function and activate these humans using optogenetic technique and kind of cure that particular symptom of this disease and that can be translated later on to the human medicine Because now the genetic is not used in human medicine medicine But to give an idea how it would look potentially already consider this example let's say we have a patient with some disease and Let's assume that we know that this is related to the malfunctioning of the neurons somewhere here. So the modern approach in trying to not help anymore is to Restore the functions of neurons by an electrical stimulation So we implant the metal electrode to that region with past electrical current and try to activate neurons by means of this electrical current It's called so called deep-brain stimulation. So the main disadvantage of this approach is that it's absolutely not Selective with respect to neurons. It activates those neurons which are Malfunctioning and also those humans which have nothing to do with that symptoms in which that with that disorder So it can cause a lot of different side effects where they don't for the person So what can we change without the genetics? Let's say we have a way to Inject the virus safely to the brain and In search of obscene to those specific neurons then we can apply light to restore the function and in this way It's going to be much more selective than just use electrical stimulation But again just to make it clear. It's like our future. Hopefully so at the moment. It's not applied good so now so I hope I can be sure that this technique is pretty cool and It's really simple in the center with extremely powerful therefore it has spread Very fast since 2005 and at the moment thousands of light users in their search, and if you try to pull it So like one of the most popular words that you will find would look like Typological breakthrough or evolution in neuroscience and so on so and basically we can say now that some dreams from That science fiction movie in 1997. So indeed come true. Thanks a lot Someone would like to ask a question So Antical problems and practical also so practical problem is that you need much stricter control how they Gene we should transport is a virus get inserted to the G normal the Person right because now in animals basically it can get inserted to more less random place Main point for us that it works expression heavens, right? We see that we get the child of soon but What can get what we can get in humans? For example that some normal GMO stop working properly or we get this cancerous tech that's you know And creation will not be controlled anymore So it means that we need to develop new virus and new technique which will be like under full control So I think that's the main problem in this Absolutely, so since already a long time people use either Electrical currents is really passing through the metal electrodes or you can also inject some chemical substance We should activate neurons as well But both of them are not specific relative to neurons, right because it affects the whole tissue which you inject and also the volume that you affect is not well controlled right because you can just Use like trial and error approach to determine how much you have to inject or how much current you need to inject to stimulate so much Right, but in any case within this volume that you can kind of adjust you stimulate all the neurons, right? So it means that you can't really assess Let's say what is a functional that particular subgroups in this volume for I don't know drinking behavior, right? because within this volume there are a lot of different types of neurons and Also axons part of following neurons you activate everything Yeah, so basically you have to plan where you make this opening right to reach Particular brain vision of course you reach like multiple on the way, right, but you cannot really go from here there You will damage too much tissue Let's say it has not been described as a paper, but as I understand that they would just start and stop start reading right It was basically that work So they really identified particular neurons which control the drinking behavior so you activate this animal Stop doing that So in this sense, they will not be a change just to the fact that animal cleaning So we don't have time Unfortunately, but well, they can just come to be your break so you can approach them and ask whatever you like