Short Wave - Why Scientists Just Mapped Every Synapse In A Fly Brain

Episode Date: March 29, 2023

To really understand the human brain, scientists say you'd have to map its wiring. The only problem: there are more than 100 trillion different connections to find, trace and characterize. But a team of scientists has made a big stride toward this goal, a complete wiring diagram of a teeny, tiny brain: the fruit fly larva. With a full map, or connectome, of the larval fruit fly brain, scientists can start to understand how behaviors shape, and are shaped by, the specific wiring of neural circuits. On today's episode, our resident neuroscience aficionado, NPR science correspondent Jon Hamilton, talks over the new findings with Short Wave co-host Emily Kwong, and explains why we big-brained humans ought to care. See pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences.NPR Privacy Policy

You're listening to Shortwave from NPR. Hey, shortwavers. Today, we have got some big news about a tiny brain, specifically the brain of a fruit fly larvae. And here to drop some knowledge is NPR's own tiny brain correspondent, John Hamilton. Hey, John. Hey, Emily. My tiny larval brain is at your service. I love it. Okay, tell us about the big news. And while you're at it, why we humans should care? The news is that scientists have created the first command. complete wiring diagram of the brain of a fruit fly larva. In other words, they've been able to map every single connection between neurons in this animal's brain.

This was published in the journal Science a few weeks ago, and it's a big deal because there are only a couple of other complete maps, and they are of much simpler brains. So the reason you and I should care is that this new map gets us closer to understanding how a human brain is wired up. Yeah, which is a big, big mystery. We don't really know much about our brains wiring, so it's amazing to think that an insect could help us understand that. Yeah, it kind of is. And actually, we're talking about an insect larva. It's this worm-like creature, you know, way smaller than a grain of rice that eventually becomes a mature fruit fly or what your biology teacher probably called Drosophila. Yes, I remember these. Fruit flies, common model organism used in biomedical research for understanding genetic fundamentals and all kinds of things. They're cool. Yeah, I mean, lots of stuff. You can understand the brain, vision, flight, sleep, all from studying fruit flies. Of course, a larval fruit fly cannot fly, but the brain of a larval dursophila is pretty sophisticated, at least compared with what you'd find in, say, a roundworm or a larval sea squirt.

And those are the only other creatures with brains that have been mapped completely. I talked about that with a brain scientist named Jovo. My name is Joshua Vogelstein. I'm an associate professor of biomedical engineering at Johns Hopkins University. And I usually go by the name Jovo. So Jovo is part of the team that was able to map every connection in the brain of a larval fruit fly. And he says this insect brain is actually a lot closer to a human brain than those other organisms that have been mapped. There's regions that correspond to decision making.

There's regions that correspond to learning. There's regions that correspond to navigation. And so lessons that we learn about foundational issues. such as how decisions are made and how learning happens, we hope that there are general principles that apply not just to the larval drosophila brain, but also essentially every other brain. Including ours. Today on the show, lessons from a very revealing maggot.

I'm Emily Kwong, and you're listening to Shortwave from NPR. So John Hamilton, today we are talking about creating wiring diagrams of the brain. First of all, what do wiring diagrams look like? And why are they such a big deal? Well, sort of imagine a very, very messy electrical circuit, right? You've got instead of transistors, you've got all these neurons. And then you have all these wires that are connecting them up together. And of course, in the brain, this is happening in in 3D. So these wires are going in and out of other things. It's a big like rat's nest of wiring. Wow. All right. And why is it such a big deal that they created one of these diagrams of a insect larva brain? Because the brain is more than just a collection of cells. It works a little bit like the Internet. You've got all these neurons, you know, which act like sort of separate computers that can send and receive information. But the amazing power and the flexibility of a brain or of the Internet comes from its wiring. It's the connections that turn all those neurons or computers into a network. Think about a huge network of computers. That is what allows Google to look in a million places to find you that perfect recipe for, say, chocolate drizzled pork rinds.

It's a thing. I checked. We have very different search history, but I admire yours. This is good. And much the same way, a huge network of neurons is what lets my brain make a good decision, like chocolate and pork, not for me. So a lot of scientists believe you have to understand that entire network. in order to figure out why we humans act the way we do. Fascinating. This is so interesting.

But if we want to understand the human brain, then why not study its connections instead of looking at the very tiny connections in an insect larva? Scientists would love to create what they call a connectome of the entire human brain. But Jovo told me it's just too complicated. Human brain has about 84 billion cells. and each one has about 10,000 connections. So if we approximate it's about 100 billion cells and 10,000-100 billion connections. That's too many zeros for me.

10,000-100 billion? That's too much. It's hundreds of trillions. It's an amazing number. And you can imagine mapping all of that is really hard. Yeah. Which is why researchers started with really simple brains. So the roundworms, sea elegans, for example,

has about 300 neurons and 7,000 connections. So by that measure, the fruit fly larva was a big step up because it has about 3,000 neurons and more than 500,000 connections. How did researchers even begin to find all of those connections? It took a whole bunch of labs in several different countries. So what they did is first they took this tiny brain from the larva and they sliced it into thousands of really thin sections.

Then they used an electron microscope to take pictures of each section. And after all that, they had to use some really sophisticated computing tools to trace each connection, you know, every synapse and create a three-dimensional map of all that wiring. Of all 500,000 neural connections? Exactly. And what did researchers find in these 500,000 neural connections? Anything surprising? One of the things they found that was surprising was that the two sides of this creature's brain are, are really pretty similar.

This all has to do with something called brain lateralization. And that's how the wiring is different on the right side of the brain and the left side of the brain. In a human brain, the right and left side specialize in different functions. So, for example, right, I mean, we've all heard of this, left brain, right brain. I've heard this, yeah. The left side of the brain tends to control speech and language. The right side does things like recognized faces. And the idea is that this makes the brain more efficient.

You can see a tiny bit of lateralization, even in the brain of a roundworm. So researchers thought a fruit fly larva might show a lot more lateralization, but the connectome they ended up with showed that there really wasn't much. There's a little, but not much. And that was a surprise. It could also help scientists figure out exactly how brain lateralization evolved over millions of years, you know, between sea slugs and humans. Yeah. John, how else is this new connectome, which is now my new favorite word, going to be used? A lot of scientists are hoping it will help them understand how the structure of the brain, you know, this wiring, is connected to the behavior of an animal or a person. Because this wiring changes over time. So, for example, if a fruit fly larva learns to associate a particular odor with a good meal, that should be reflected in changes in its connectome.

But Jovo told me you can only study that sort of phenomenon if you have a starting point, you know, a baseline connectome for the animal. What it allows us to do is now, say, train a different larval drosophila on some behavior, get its connectome and compare. Or look at differences across gender or differences across species or differences across developmental stages. This is the landmark first reference that we can use to compare everything else. Yeah. Yeah, it's such a stepping stone towards more information. And it sounds like we're going to need many more connect domes to understand our human brain. Yeah, a lot more.

And from bigger brains. But that is happening. You know, the National Institutes of Health is putting a lot of money into creating a full connect dome of a mouse brain. A lot of that research is taking place at the Alvin Institute in Seattle. And what they've already done shows just how difficult it is to map even a mouse brain. Oh, yeah, they're a lot bigger than fruit flies. Yeah. So far, the researchers at Allent Institute have created a connectome for only a one millimeter

cube of a mouse brain. Oh, that's so small. Right. It is a tiny fraction of the whole brain. And so I talked to Nuno Maserico de Costa, and he's one of the scientists involved in that research. For our millimeter cube, we have to cut 30,000 sections. That was a day and night adventure for 12 days where our team just took shifts. So how do we section this object that is much larger is something that is still not

solved and we and others are working on? This kind of science, whenever I hear about it, it's just mind-blowing. The amount of dedication, the amount of time, the amount of teamwork, it sounds like even a complete map of a mouse brain is a few years off. If they've only done one millimeter cube. It is. Nuno told me that 10-year time frame is probably what. he's thinking. But, you know, there are a lot of researchers who think connectomes like this one have the potential to solve some really tough problems in neuroscience. Nuno says that on a very practical level, a connectome of the human brain might show which circuits are altered in conditions like autism or schizophrenia. And then there is this other part, which is that

every idea, every memory, every movement, every decision you ever made comes from the activity of neurons in your brain. And this activity is an expression of this structure. So what we hope is that if we have some map of that structure, will be in a better position to understand it. What we're saying here is it could basically help us explain what makes us us. A very worthy goal. John, thank you so much for coming on to talk about this with us.

Anytime, Emily. Before we head out, we want to take a minute to talk about it. about Shortwave Plus. Plus subscribers help make shows like this one even possible. And they also get to listen to all of our episodes without any sponsor breaks. Find out more at plus.npr.org slash shortwave. And to everyone who's already subscribed, we appreciate you. We see you. Thank you so much. This episode was produced by Burley McCoy. It was edited by Gabriel Spitzer and fact checked by Anil Oza. The audio engineer was Gilly Moon.

Brendan Crump is our podcast coordinator. Beth Donovan is the senior director of programming, and Anya Grundman is the senior vice president of programming. I'm Emily Kwong. And I'm John Hamilton. Thanks for listening to Shortwave from NPR.