The first wiring map of an insect's brain hints at incredible complexity

By Jon Hamilton

Published March 9, 2023 at 6:08 PM EST

What looks like a pin-headed critter on the right is actually a larval version of the fruit fly on the left. Both have remarkably complex brains, scientists say, with different regions devoted to decision-making, learning and navigation.

Scientists have created the first detailed wiring diagram of an insect brain.

The brain, from a fruit fly larva, contained 3016 neurons connected by 548,000 synapses, the team reported Thursday in the journal Science.

Previous wiring diagrams, known as connectomes, were limited to worms and tadpoles with just a few hundred neurons and a few thousand synaptic connections.

The fruit fly larva connectome is an important advance because it's "closer in many regards to a human brain than the other ones," says Joshua Vogelstein, an author of the study and an associate professor of biomedical engineering at Johns Hopkins University.

For example, "there's regions that correspond to decision making, there's regions that correspond to learning, there's regions that correspond to navigation," Vogelstein says.

But the challenges scientists faced in producing the fruit fly larva connectome show just how far they still have to go to map a human brain, which contains more than 80 billion neurons and hundreds of trillions of synapses.

"The brain is the physical object that makes us who we are"

Researchers have focused on connectomes because a brain is so much more than just a collection of neurons.

"The brain is the physical object that makes us who we are, Vogelstein says. And to fully understand that object, he says, you need to know how it's wired.

Mapping the complete human connectome is still many years off. So in the meantime, researchers hope this new wiring map of the fruit fly can offers clues to how all brains learn, for example, and remember, and control an animal's behavior.

The brain of a fruit fly larva, like a human brain, has a right and left side. But when researchers mapped the connections in the insect brain, "one surprise [was] how similar the right and the left sides are," Vogelstein says.

In humans, the right and left sides of the brain can have very different wiring. Circuits involved in speech tend to be on the left, for example, while circuits that recognize faces tend to be on the right.

A "landmark first reference"

The new map will help scientists study the ways learning changes the brain, how brain wiring differs by sex, and how wiring changes during an animal's development.

"This is the landmark first reference that we can use to compare everything else," Vogelstein says.

This complete map of neural connections took a large team more than a decade to finish, and involved painstaking science.

The team began by slicing a single tiny brain the size of a grain of salt into thousands of very thin sections.

"You don't screw it up at all because if you make one mistake you have to basically throw out the entire brain and start all over again," Vogelstein says.

The team used an electron microscope to capture an image of each slice. Tracing the connections from one neuron to another required powerful computers and specialized computational tools.

Those tools are enough to trace millions of connections, Vogelstein explains, but not the trillions of connections found in a human brain.

So researchers at the Allen Institute in Seattle are working on an easier next goal: mapping the connectome of a mouse. And even that is a huge challenge, says Nuno Maçarico da Costa, an associate investigator at the Allen Institute in Seattle who was not involved in the study on fruit fly larvae..

"We started by trying to map the connectivity of a millimeter cube of mouse cortex, which is kind of a grain of sand but has one billion connections —– 100,000 neurons, and 4 kilometers of cable," da Costa says.

It took 12 days just to slice up that one tiny cube, which represents about only about one five-hundredth of a complete mouse brain, he says.

Despite the difficulty, mapping more complex brains is worth the effort, da Costa says, because it could eventually help scientists understand how a human brain can be affected by disorders like schizophrenia.

"If your radio breaks," da Costa says, "if someone has a wiring diagram of your radio, they'll be in a better position to fix it."

A human connectome will also help scientists answer some basic questions, like how we learn and why we behave the way we do, he says.

"Every idea, every memory, every movement, every decision you ever made comes from the activity of neurons in your brain," da Costa says. "And this activity is an expression of this structure."