03/31/2023

The First Fully Mapped Animal Brain Is The Larva Of A Fruit Fly

7:52 minutes

a colorful brain scan of a fruit fly. there are two main lobes bulbous in shape that are filled with colored little balls, which represent neurons. there are long filaments stringing down from the lobes
The complete set of neurons in an insect brain, which were reconstructed using synapse-resolution electron microscopy. Credit: Johns Hopkins University/University of Cambridge

Understanding how a brain works is one of the most challenging tasks in science. One of the ultimate goals in brain research is to develop brain maps, which catalog which neurons are connected to others, and where. If researchers have a brain map, they can better understand neurological conditions like addiction, and develop more effective treatments. It may even help scientists understand more abstract concepts, like consciousness. 

The catch? Mapping millions, or even billions, of tiny little neurons is an extremely challenging and expensive task. 

But a team of researchers at Johns Hopkins University recently completed a 12-year effort to map the entire brain of a fruit fly larva, which is the size of a grain of salt, and contains 3,000 neurons and 500,000 connections. Their results were published in the journal Science.

Joining guest host Shahla Farzan is the paper’s senior author Joshua Vogelstein, an associate professor of biomedical engineering at Johns Hopkins University. They talk about how exactly his team completed this task, when a human brain map might be completed, and how this could be a meaningful step in understanding how enlightenment works. 

This video moves through cross-sections of the brain to reveal the final reconstructed neurons. Credit: Johns Hopkins University/University of Cambridge


Segment Guests

Joshua Vogelstein

Dr. Joshua Vogelstein is an associate professor of Biomedical Engineering at Johns Hopkins University in Baltimore, Maryland.

Segment Transcript

SHAHLA FARZAN: One of science’s greatest challenges is understanding how exactly the brain works. Knowing how a brain is wired would not only help researchers better understand certain neurological conditions, but it could also help shed light on age-old philosophical questions about consciousness. But to get to that next level, researchers need to develop detailed brain maps for different animals showing where each nerve cell is connected, like a wiring diagram. The catch? Even mapping teeny tiny brains like those of insects is incredibly difficult, time consuming, and expensive.

But a team of researchers at Johns Hopkins University recently completed a 12-year effort to map the entire brain of a fruit fly larva. Their findings were published in the journal Science. Joining me is one of the lead authors on that paper, Dr. Joshua Vogelstein, an associate professor of biomedical engineering at Johns Hopkins University based in Baltimore Maryland. Welcome to Science Friday.

JOSHUA VOGELSTEIN: Thank you so much for having me.

SHAHLA FARZAN: So why is it so important to map the brain?

JOSHUA VOGELSTEIN: Well, our brains are involved in every thought we have, every decision we make, and everything we learn. So my perspective is if we want to truly understand who we are and our role in the universe, we’re going to have to understand how our brain works. And part of that is understanding which parts of the brain are connected to which other parts.

SHAHLA FARZAN: So your main goal with this project was to map out what’s known as the connectome of a fruit fly brain, which I’m guessing is a word that not many people have heard before. Can you just describe for us briefly what that is and why it’s important to understand it?

JOSHUA VOGELSTEIN: Yeah, so a connectome is a set of connections between every neuron in our brain. So humans have 100 billion neurons and 1,000 trillion connections. So the connectome for a human would include all of those connections. We’re not able to do that yet with a human, but we have been able to do it with a little fruit fly which has only 3,000 neurons and half a million connections. The reason it’s so important is because all of the thoughts we have, all of the decisions we make, all of the feelings we feel, all depend on our brain.

And it all depends on information flowing across the neurons. And the way they do that is through the connections, so if we understand these connections better we’ll be able to better understand ourselves and be able to help ourselves more if we have any kind of mental illness, or any issues with learning. Or even if we just want to be able to think more clearly, learn more effectively, the connectome, we believe, can help serve all of those purposes.

So think about addiction. We want to understand what changes in someone’s brain when they’re addicted to say cigarettes or opioids. And we currently believe that what’s happening in humans’ brains is probably very similar in certain ways to what’s happening in a fly brain. So what we could do is we could cause some flies to be addicted to something, and now we can look at how their brains are different from those who are not addicted. And that will tell us the mechanism of what changes to make them addicted. From there, we can extrapolate and try to understand how that affects the humans and what we could do to help prevent that from happening or how to treat it if it has happened.

SHAHLA FARZAN: OK, that makes sense. So thinking about this particular project, it took you and your colleagues about 12 years, as we mentioned, to map the brain of a fruit fly larva. How exactly did you do this?

JOSHUA VOGELSTEIN: Yeah, so the first step was to slice up this little itty bitty brain into thousands of even littler itty bitty slices. Then we had to use a microscope to image and take thousands of megabytes of images to build this three-dimensional picture of the brain. Once we had that, then we had about 50 people all day every day drawing lines in this image to show which neurons were connected to other neurons. That process took a few years. Then we had to proofread and error correct all of that, which took another few years.

And finally, we got to the fun part for me, which is the part I was involved with, which is understanding what was actually going on and seeing what we can say about brains once we have this.

SHAHLA FARZAN: Wow. OK, 50 people putting in full-time work on this project. that’s a huge amount of work done.

JOSHUA VOGELSTEIN: Massive undertaking. It was the largest brain ever done. This is the first brain that we’ve ever mapped as a species.

SHAHLA FARZAN: That’s incredible. And I have to ask, I mean, we’re talking about a brain that’s smaller than the size of a grain of salt. How did you slice it up? I’m imagining something that is like the world’s tiniest meat slicer.

JOSHUA VOGELSTEIN: (LAUGHING) That’s basically what it is. It’s a tiny meat slicer. And it’s it is meat, it’s a brain.

SHAHLA FARZAN: That’s incredible. So can you just briefly describe for us what does this brain map look like?

JOSHUA VOGELSTEIN: So we wrote software that would let us navigate across brain regions, just like one would do if you’re driving around the city and just like Google maps. The first thing it had is just a fixed structure, which roads connect to which other roads. But then Google added other things. You have street view, and you have traffic patterns. And so we’re not adding all of those things on top of the map that we have, but for the brain. So we’re adding what the neurons are. Like does this one have dopamine? And does this one have something else? And that helps us understand and address diseases and things like that?

SHAHLA FARZAN: So why fruit fly larvae? Why map that particular brain out of all the brains in the world?

JOSHUA VOGELSTEIN: Well, to be totally honest, it was the biggest one we could do at the time. The next biggest one that we’re interested in would be an adult fruit fly. That will be done soon, but that takes a whole other team of many years of many people.

SHAHLA FARZAN: So you mentioned that the ultimate goal of this is to really understand the human brain. Are people trying to map the human brain right now? Or is that just still too hard to do?

JOSHUA VOGELSTEIN: We are involved in lots of efforts to map the human brain. We don’t yet have the technology that would enable us to trace every single neuron and find every single connection. Instead, we use technology like MRI, and it tells us basically which regions of the brain are connected to each other but not which neurons are connected to each other.

SHAHLA FARZAN: So it sounds like that particular goal is still a ways off to try to map the human brain– completely at least.

JOSHUA VOGELSTEIN: Oh yeah, so people are talking about doing a mouse next. And that project is slated to take about a decade and cost about $1,000,000,000.

SHAHLA FARZAN: Wow. So one of your research interests is understanding enlightenment. Can you tell us how mapping the brain, especially an insect brain like this, could help us better understand that?

JOSHUA VOGELSTEIN: Sure. So my perspective is that when those of us are able to achieve states of enlightenment, that corresponds to something happening in our brain, just like any other state we have of fear or anger or dreaming or any of those things. And so what I want to understand is what it is that’s happening for people when they’re achieving state of enlightenment. What’s happening in their brain? And more importantly, how can we develop the technology to support people so that they can change their brains in such a way as to feel more peaceful and more serene with their life in the situation that they have.

SHAHLA FARZAN: Amazing I think that’s a great note to end on. That was Joshua Vogelstein, associate professor of biomedical engineering at Johns Hopkins University. Thanks so much for taking the time.

JOSHUA VOGELSTEIN: Thank you so much for having me.

SHAHLA FARZAN: And you can check out some beautiful photos of the fruit fly brain map at sciencefriday.com/bugbrain.

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About D Peterschmidt

D Peterschmidt is a producer, host of the podcast Universe of Art, and composes music for Science Friday’s podcasts. Their D&D character is a clumsy bard named Chip Chap Chopman.

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