Scientists complete first map of an insect brain

Researchers have completed the most advanced brain map to date, that of an insect, a landmark achievement in neuroscience that brings scientists closer to true understanding of the mechanism of thought.

The international team led by Johns Hopkins University and the University of Cambridge produced a breathtakingly detailed diagram tracing every neural connection in the brain of a larval fruit fly, an archetypal scientific model with brains comparable to humans.

The work, likely to underpin future brain research and to inspire new machine learning architectures, appears today in the journal Science.

"If we want to understand who we are and how we think, part of that is understanding the mechanism of thought," said senior author Joshua T. Vogelstein, a Johns Hopkins biomedical engineer who specializes in data-driven projects including connectomics, the study of nervous system connections. "And the key to that is knowing how neurons connect with each other."

The first attempt at mapping a brain -- a 14-year study of the roundworm begun in the 1970s, resulted in a partial map and a Nobel Prize. Since then, partial connectomes have been mapped in many systems, including flies, mice, and even humans, but these reconstructions typically only represent only a tiny fraction of the total brain. Comprehensive connectomes have only been generated for several small species with a few hundred to a few thousand neurons in their bodies-a roundworm, a larval sea squirt, and a larval marine annelid worm.

This team's connectome of a baby fruit fly, Drosophila melanogaster larva, is the most complete as well as the most expansive map of an entire insect brain ever completed. It includes 3,016 neurons and every connection between them: 548,000.

"It's been 50 years and this is the first brain connectome. It's a flag in the sand that we can do this," Vogelstein said. "Everything has been working up to this."

Mapping whole brains is difficult and extremely time-consuming, even with the best modern technology. Getting a complete cellular-level picture of a brain requires slicing the brain into hundreds or thousands of individual tissue samples, all of which have to be imaged with electron microscopes before the painstaking process of reconstructing all those pieces, neuron by neuron, into a full, accurate portrait of a brain. It took more than a decade to do that with the baby fruit fly. The brain of a mouse is estimated to be a million times larger than that of a baby fruit fly, meaning the chance of mapping anything close to a human brain isn't likely in the near future, maybe not even in our lifetimes.

The team purposely chose the fruit fly larva because, for an insect, the species shares much of its fundamental biology with humans, including a comparable genetic foundation. It also has rich learning and decision-making behaviors, making it a useful model organism in neuroscience. And for practical purposes, its relatively compact brain can be imaged and its circuits reconstructed within a reasonable time frame.

Even so, the work took the University of Cambridge and Johns Hopkins 12 years. The imaging alone took about a day per neuron.

Cambridge researchers created the high-resolution images of the brain and manually studied them to find individual neurons, rigorously tracing each one and linking their synaptic connections.

Cambridge handed off the data to Johns Hopkins, where the team spent more than three years using original code they created to analyze the brain's connectivity. The Johns Hopkins team developed techniques to find groups of neurons based on shared connectivity patterns, and then analyzed how information could propagate through the brain.

In the end, the full team charted every neuron and every connection, and categorized each neuron by the role it plays in the brain. They found that the brain's busiest circuits were those that led to and away from neurons of the learning center.

The methods Johns Hopkins developed are applicable to any brain connection project, and their code is available to whoever attempts to map an even larger animal brain, Vogelstein said, adding that despite the challenges, scientists are expected to take on the mouse, possibly within the next decade. Other teams are already working on a map of the adult fruit fly brain. Co-first author Benjamin Pedigo, a Johns Hopkins doctoral candidate in Biomedical Engineering, expects the team's code could help reveal important comparisons between connections in the adult and larval brain. As connectomes are generated for more larva and from other related species, Pedigo expects their analysis techniques could lead to better understanding of variations in brain wiring.

The fruit fly larva work showed circuit features that were strikingly reminiscent of prominent and powerful machine learning architectures. The team expects continued study will reveal even more computational principles and potentially inspire new artificial intelligence systems.

"What we learned about code for fruit flies will have implications for the code for humans," Vogelstein said. "That's what we want to understand -- how to write a program that leads to a human brain network."

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Scientists find previously unknown jumping behavior in insects

A team of researchers has discovered a jumping behavior that is entirely new to insect larvae, and there is evidence that it is occurring in a range of species -- we just haven't noticed it before.

The previously unrecorded behavior occurs in the larvae of a species of lined flat bark beetle (Laemophloeus biguttatus). Specifically, the larvae are able to spring into the air, with each larva curling itself into a loop as it leaps forward. What makes these leaps unique is how the larvae are able to pull it off.

"Jumping at all is exceedingly rare in the larvae of beetle species, and the mechanism they use to execute their leaps is -- as far as we can tell -- previously unrecorded in any insect larvae," says Matt Bertone, corresponding author of a paper on the discovery and director of North Carolina State University's Plant Disease and Insect Clinic.

While there are other insect species that are capable of making prodigious leaps, they rely on something called a "latch-mediated spring actuation mechanism." This means that they essentially have two parts of their body latch onto each other while the insect exerts force, building up a significant amount of energy. The insect then unlatches the two parts, releasing all of that energy at once, allowing it to spring off the ground.

"What makes the L. biguttatus so remarkable is that it makes these leaps without latching two parts of its body together," Bertone says. "Instead, it uses claws on its legs to grip the ground while it builds up that potential energy -- and once those claws release their hold on the ground, that potential energy is converted into kinetic energy, launching it skyward."

The discovery of the behavior was somewhat serendipitous. Bertone had collected a variety of insect samples from a rotting tree near his lab in order to photograph them when he noticed that these beetle larvae appeared to be hopping.

Bertone and paper co-author Adrian Smith then decided to film the behavior in order to get a better look at what was going on. That's when they began to understand just how peculiar the behavior was. Smith is a research assistant professor of biological sciences at NC State and head of the Evolutionary Biology & Behavior Research Lab at the North Carolina Museum of Natural Sciences.

"The way these larvae were jumping was impressive at first, but we didn't immediately understand how unique it was," Bertone says. "We then shared it with a number of beetle experts around the country, and none of them had seen the jumping behavior before. That's when we realized we needed to take a closer look at just how the larvae was doing what it was doing."

To determine how L. biguttatus was able to execute its acrobatics, the researchers filmed the jumps at speeds of up to 60,000 frames per second. This allowed them to capture all of the external movements associated with the jumps, and suggested that the legs were essentially creating a latching mechanism with the ground.

The researchers also conducted a muscle mass assessment to determine whether it was possible for the larvae to make their leaps using just their muscles, as opposed to using a latch mechanism to store energy. They found that the larvae lacked sufficient muscle to hurl themselves into the air as far or as fast as they had been filmed jumping. Ergo, latching onto the ground was the only way the larvae could pull off their aerial feats.

Meanwhile, in an unrelated video about jumping maggots, Smith had included a short clip of the jumping behavior in L. biguttatus. That video was seen by a researcher in Japan named Takahiro Yoshida, who had witnessed similar jumps in the larvae of another beetle species called Placonotus testaceus, but had not published anything related to the behavior.

"We don't have high-speed footage of P. testaceus, but the video evidence we do have from Yoshida's lab suggests that this previously unknown behavior is found in two different genera which are not even closely related," Bertone says.

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