Mapping the Nervous System

what with the mountains and the oceans. Now, we're not gonna talk about the political borders. I'm not going to talk about cartographers here. We're going to talk about maps of nervous systems, which is has a specific name, a connect home. Now what a connect home that I don't know. It's CEO in an E C T O M E. What on earth is that thing? It looks like it's

connect to me? But it's what I was thinking. Honestly, I actually watched a Ted talk and I'm just going to pronounce it the same way the fellow did, so connect them. What it is is, it's a a complete neural map of an organism's neurons. So think of it like a wiring diagram. If you were an electrician and you need to have a diagram of a wiring system. It's like that, except for the nervous system of an

actual organism. Now, to have a true connect dome, you need it to be three dimensional, because we are not two dimensional creatures, you know, so you wouldn't want to have just a flat representation. Most of us. See, most of us are are well rounded individuals. Everyone in this room is, certainly, So you want to have a three dimensional uh ability, you know, you want to be able to depict it in three dimensions so that you have

an accurate look at what this nervous system is. And it's supposed to show all the neurons and connections between them within our an organism. So surely we have not done this to an actual organism as we have. Only one has a complete connect dome of all of its neurons, and that would be Senor Rhabditis elegance or see elegans also known as worm teeny tiny worm. Um. Yeah, it only has three hundred two neurons, so yeah, not not You're like totally like, I'm not impressed by this groundbreaking

scientific discovery. Take that scientists deal with my puff. Three neurons is a tiny amount comparatively speaking, but we'll get to that. So scientists began to study these worms in an effort to understand neurology better, among other things. I mean, of course, scientists all over the place like like worms. I mean, who doesn't, but they these particular scientists were interested in studying the worms to to create a connect home, and they figured that this was a good place to start.

So back in the nineteen seventies you had a team that was looking into it, and it wasn't until nineteen eighties six that they were able to publish the first prelimit arey connect home for this worm. And more than twenty years after that you had a second team produce a much more complete connect home, a more accurate representation of the connect home. So it is a very slow process. And that's just three neurons, right, It's not that many

comparatively speaking. And then this year two thou fourteen, in May, another team published a paper about creating a real time three D map of this worm's neural system and action, meaning you could see the impulses moving up and down the length of this worm as its nervous system was taking over for any anything like from detecting stimuli to sending the information up to the ganglia to reacting to it.

Uh it was. This is what's really the groundbreaking. I mean, all of its groundbreaking, but this is really ground baking breaking stuff. You're talking about being able to get a real time view of what's going on within the nervous system of an organism. I can't even imagine how one would do that. Well, you don't have to imagine, because someone I will tell you. Uh no, this was really

an interesting idea. So within this worm's nervous system, essentially what's going on is neurons are passing information in the form of calcium ions. So these calcium ions are passing from one neuron to the next, right chemical electrochemical transaction exactly. So if you go with this calcium ion, if you're able to make it stand out in some way and then you're able to actually capture that information, you can see what's going on. So they developed some fluorescent bio markers.

So essentially this is just meaningless information that glows. So it's it's not meant to harm the organism in any way. You want it to to keep everything intact, but it ends up marking those calcium in It glows specifically when it binds with a calcium ion exactly, so that way, when this is going on, the scientist can see it now.

Of cour, just making the worms have little calcium ions like glow doesn't mean that they're going to be able to see everything that's going on, right, I mean, you're not gonna be standing there looking at a worm thinking, well, there's a flash of light. It's thinking something that's That's another way it works that I would have gotten to be fair. To be fair, worms aren't really thinking that much anyway. So if it wasn't sparking, you'd just be thinking, well,

we got a particularly stupid worm. Oh look, he's contemplating consubjection to like this. This worm is obviously a fan of Nietzchi, a scholar. I like that. We're all just gonna start let's just keep on naming various thinkers. So what are you going to do about that? You know,

if the worm doesn't think, it just disappears anyway. The scientists decided that the way to capture all this information because obviously if you used a regular light microscope, even if it was powerful enough to detect those calcium ions that are glowing, you would still only have a two dimensional representation of what was happening. Right, You're not getting any depth there. So how do you get the depth? And that they managed to do through a technique called

light field deconvolution micross scope. What I know, I love different kinds of microscope. I do too. No, I'm not joking. I really do believe that was my cross could be treats a snap crack on pop. Well no, okay, no, I'm serious. So I grew up with a little, uh kind of cruddy micro microscope that I would stare through. I'd i'd stay in a little pain and put some kind of junk on there and look at it. But everything just looked like gray squiggles, you know, because it

was that back lip microscope we've all seen before. It's you got the light coming up the tube from the bottom and you see this two dimensional cross section that's not very colorful. It's wonderful now that we have all these techniques to see three dimensional shapes at the micro level, right, and light field. This is something you guys might have heard about, in fact that we may have even talked about in the past. Uh, you've heard of light field photography,

which is what the lightrous camera uses. This is the idea of upturing information by not just the fact that there's light there, but capturing the direction of light, the rays of light within a scene. So you're capturing all the light that is within the scope of that camera. Now, with a litros camera, what this means is that when you take a picture, you can change the focal point

of that picture after it's been taken. So i have Lauren standing in the foreground, and I've got Joe way off in the background, and I take a picture, and at first laurens and focused, Joe's not. But if I tap on Joe, he suddenly becomes in focus and Lauren goes out of focus, and it's it's dynamic. I can change.

I can pick the focal point within the picture and change it because it's captured all of the information, as opposed to your classic photography, which is stuck with whatever the focal point of the lens was at the moment you took the picture. Sure um in the specific case,

of this light field. Deconvolution microscopy the the ideas that you're using, rather than the single lens that Joe is talking about through traditional microscopy, an array of lenses that refract and collect a single point of light, thereby letting you get a good idea of where that little blip

is in three dimensional space. Right, So now you've got this more complete look at all these different blips within this three dimensional space while you do next, Well, that doesn't really help you out that much unless you then send it to a computer running special software which is taking all this information, crunching it and then forming a three dimensional map of that worm's nervous system and then showing the actual activity via the little florescent calcium ions.

While the worm, you know, does normal worms stuff or um or abnormal worms, or or is it supposed to a to a sort or a smell of some kind. So yeah, if you were to give some kind of stimuli that ends up making the worm react in some way, right, it's it's exposed to a book of Nietzsche that has decomposing pages that can eat. That would be probably the best kind of Nietici for this particular type of worm.

But yes, so you're exactly right. You would be able to see by the reaction in the nervous system what is going on inside the worm. Not necessarily understand it, but you would be able to see it. You know, keep in mind these are this is an important step, but it's just a step. Well, we'll go into more about the implications in a little bit, but this complex software has to crunch all that put up the map, and it's more or less it's it's on a millisecond scale.

It's something like fifty images per second, which is pretty cool, yeah, but still not if you think of time as resolution in the sense it's a low resolution image. So it's not resolution in the sense of of how many pixels or whatever, or how sharp the picture is, but rather how how accurate is it over time? And it's a time scale that's too slow for it to be uh, you know, it's not advanced enough for it for us

to call it true real time. It's really good. But I think what we're going to see is we're going to see more development in computer software and this technology where we'll start to have an even uh more elongated time scale, will get down to like nanosecond level. It's

which will be especially important for things more complex than worms. Now, in order to do all that number crunching, you can't just use one computer because it actually is so um intense that they have to use grid computing for it. So they're using using multiple computers to solve problems in parallel, so each computer is taking a little bit of the work.

And we've talked about this in the past two about how you use a distributed computing system in order to divide up a big task into lots of smaller tasks, which makes it more manageable. Otherwise you would have to have the world's fastest computer, and even that might be slower than a grid of computers working in this way. But as long as your problems don't have to be solved sequentially like that, that solving number two doesn't depend on solving number one, you can split them up, right.

So that's pretty awesome, this idea of being able to see what's going on with the neurons inside a worm. But um, what else could we look at? So so three neurons, yeah, what about something that has like a hundred billion neurons or conservatively eighty billion neurons? Okay, Uh, that's a tall order because this this this team the best that they've done beyond the worm, and not to I'm not trying to suggest that they haven't done their work.

This is yeah. But the other thing they did was they imaged about half of a zebra fish's neurons larva's larva's thank you. Yes, the zebrafish lava not an actual zebra fish, but the zebra fish larva and the zebrafish lava have about ten thousand neurons, so they were able to image five thousand of those. Um And there's some other examples of organisms that we've managed to create partial connectomes, for example, the retina's and visual cortex of a mouse.

Well those have been completed or mostly complete, I shouldn't say completed, partially completed. When you're talking about humans, it's eighty two hundred billion neurons, something like a hundred trill allion synapses connecting all those neurons and various configurations. Orders of magnitude does not do this justice, right. You can't

just say it's a couple of orders of magnitude. No, it's it's an enormous jump from worm to a person for most people anyway, would it be fair to say that the problem represented by doing the same kind of thing with a brain on the scale of a human brain is not just like a scaling up problem. It's like it's another ballpark entirely. It's not like we just need a little more power. It's like we're not We're

not even close. Yeah, I mean, the closest we've got is is working our way towards building a connect them. Not a real time three dimensional moving picture, right, you know, the one with the worm you're actually able to watch it's not thought, but you're able to watch impulses as they move throughout the worm's body. With the humans, the closest we're getting is the Human Connectome project is the best known one. But this is just to create that

neural map. And I think it's something like participants for the entire program for this particular approach. And this is a five year mission, which is all of our Star Trek fans out there, which began in two thousand nine, July two thousand nine, So we're getting up there kissing

the connect home. So at any rate, Uh, this is a collaboration between a few different um research facilities, the two main ones being the Laboratory of neuro Image Imaging at u c l A and the Martino Center for Biomedical Imaging at Massachusetts General Hospital and UH it's sponsored in part by the National Institutes of Health, and so this is an interesting approach again trying to create a

neural map of human beings. It's not again, it's not a real time representation, but just to actually map out all the neurons and synapses at alone is an incredibly huge task. So they had to start commissioning new types of technology and software to be able to try and tackle this problem, and one of those was a super scanner from Siemens, and Siemens makes all sorts of different UH high grade technology equipment. In this case, they were using a m r I that did does three different

types of m r I in one go. It does a diffusion tensor imaging, diffusion spectrum imaging, and high angular resolution diffusion imaging also known as HARDY, So all of that's different types of magnetic resonance and imaging. Mri I type stuff does it so that it can get the

most um complete picture of a person's nervous system. And UH the literature that is available on the human Connectome Projects shows pictures of these things and they do look like something straight out of you know, Star Trek or Star Wars or something like that. Uh, And they talk about how this this equipment, while it's very useful for this regular project, will also be incredibly useful for numerous

medical applications from this point forward. So it's not like this was a piece of equipment that was made for this one and only one thing and after that, you know, that's, well, that was cool. It's actually gonna be useful long after this project has concluded, so that's kind of cool. Um. Now, on the computer side, they're also using grid computing to run all this stuff and make sure that they can process all the information in order to actually come up

with the results. So you know, you think about it, if you're looking to map eighty to a hundred billion uh little tiny neurons, like you need to map all of those and then all their connections, even if it's not, you know, as complex as you would first imagine, just the number alone means that that's a lot of data. So that's why you have to have this kind of grid computing approach or else it just wouldn't work. So that's kind of interesting. I'd like to, you know, read

up on it more. Um, there is a website for the Human Connect Home project. It is not perhaps the most flashy or um sophisticated website I've ever seen, but it's certainly effective. So I am interested to see what I mean. I was able to understand everything, so that that was good. There wasn't a little image of a man in a construction hat saying, you know, like, website under development, so that was good. But there was a dancing baby. There was a midi of a sa base.

I don't know why. No, I'm just kidding. I'm just kidding. But yeah, I'll be really curious to see what all the the outcomes are of this project when it concludes. I am assuming they're going to publish a lot. So I want to play Devil's advocate because, as you all know, I like all I'm someone who likes building weird things that don't have an obvious benefit to the lay person, or sometimes an obvious detriment. Crunch kicking robot was that

was that? It was? I didn't know alright, no, no, no no, okay, no, imagine I'm the lay person who says, what are you going to use that for all right, Well, that's a good question. What difference does it make. I mean, it's a worm brain, so from just going from the worm so we're not even talking about human connect Home project. We're just talking about that three dimensional look at the worm's nervous system. It tells us more about how nervous

systems in general work. This is an area that we know very little about in the grand scheme of things we know. What we know is that we don't know a lot, right. We do understand some things. We understand some of the very basic things that are happening, but we don't understand how they're working necessarily across an entire system all at once. The way I'd phrase it, though obviously I'm no neuroscientists, the way I understand it is that we have a lot of observations, but we don't

know what they mean. And this is another step getting closer towards understanding the meaning behind what we've observed. Doesn't mean that we're obviously that the lightbulb has come on and now everything makes sense, but it's the only way for us to get to that understanding is to continue making observations and to continue doing experimentation in order to really get an idea of what's going on and why

it's happening the way it is. And the closer we get to mapping out nervous systems, the more will understand everything from basic functions of a healthy uh, you know, human brain to any sort of dysfunctional activity. So whether that's from brain damage or from any of a number of neurological diseases or disorders, or or or even from from mental health disorders. Yeah, I've seen a lot of

discussion about the Human connect On project. One of its goals is to study things like, uh, people who suffer from schizophrenia and to see what what is different about their nervous systems compared to someone who does not suffer from schizophrenia, and perhaps through understanding these sort of dysfunctions, we might be able to address them or perhaps even cure them in the future. Now granted all of that. Yeah, and when you say in the future, you're talking about

a good distance into the future. We're not talking about something that's going to turn around and happen within the next six months. I want to be clear about that, because, yeah, we mean whenever you read these reports. You know, people like the people who write the reports. Not everybody, but some people fall into that kind of easy journalism trap where you say this will lead to curing mental illness. It's it's possible that let me put it this way, if we don't do these steps, it will be a

lot harder to do it. But this, this may or may not lead us down that pathway, but certainly if we don't do the work, we won't get there. So another thing that could possibly happen way off into the future, sure, is that by understanding more about how these neural pathways work in organisms, we could create a synthetic creature, whether

that's biological or whether it's compurely electronic. We might be able to create a synthetic intelligence by learning more about how our intelligence works, or or build that that brain like computer that we were talking about a few episodes ago. Yeah, so that's another thing that's a possibility. Again, it is not necessarily true that what we're doing today or what these scientists are doing today, will be a direct path from A to B that leads there, but it could

very well be. That's an important step along the journey. So, uh, you know, I always hate making big predictions and saying, oh, and in ten years, we're going to have these thinking computers and mental mental illness will be a thing of the past. I certainly hope that is true. But what I am really excited about is seeing more developments in this kind of research and finding out what else we learned, because again, as we've said multiple times on this podcast,

learning is great. I mean, the more you learn, the better off you are. And so, uh, we were fully in favor of it, even if it is something as silly as mapping out a worms nervous system and learning that it doesn't have a taste for Nietzsche, even if the book is rotting so at any rate, Uh, just those chemical treated pages there, I tell you. You know, the odd thing was totally went for the Kindle version. So uh yeah, that wraps up this discussion on just

the mapping of the nervous system. It's a really cool project. Go ahead and check out the Human connect Home project and also look around at some of the stories about the the various projects that have gone into trying to map out this worm's nervous system. I mean that that alone is interesting. I mean, imagine they started in the seventies, and it wasn't until they were able to publish the first rudimentary connect home that just with three two neurons.

It just proves how complex this is. And then you know, again that leap to human big leap for most people. I know a few people who comparison to worms not that off base. Alright, So guys, if you have any suggestions for future episodes a Forward Thinking, I'm not looking at anyone in this room. I just love how you always pepper our optimistic view of the future with some really antisocial commentary. I made the same I made the same joke in the video so um, but I've never

stopped me before, right, I'll tell the same jokelations. Thank you. I have a very specific role to fill in this world now. If you have any suggestions for future episodes off Forward Thinking, if you want to hear more about the amazing brain, or there's just something else that really fascinates you and you wonder what it's going to be like in the future, you should let us know and

we will be happy to tackle that subject. You can contact us through Twitter or Facebook or Google Plus are handled all three f W Thinking, or you can send a good Ole Fashion Email That address is FW thinking at discovery dot com and we'll talk to you again really soon. For more on this topic and the future of technology, visit forward thinking dot com, brought to you by Toyota. Let's Go Places,