The brain of an adult fruit fly has been mapped—the human brain can follow suit. peppermint

Fruit flies are smart. For starters—the hint is in the name—they can fly. They may also flirt; fight; form complex, long-term memories of your surroundings; And even warn each other about the presence of unseen threats such as parasitic wasps.

They perform each of these tasks based on sophisticated processing of sound, smell, touch, and vision, organized and operated by a brain made up of about 140,000 neurons – more than the 300 found in nematode worms, but far fewer than that. 86 billion of a human brain, or 70 million of a rat. This well-established but non-trivial level of complexity has made fruit flies an attractive target for those who want to build a “connectome” of an animal’s brain – a three-dimensional map of all its neurons and the connections between them. . This fascination is further enhanced by fruit flies being already one of the most studied and best understood animals on Earth.

For many years the race to assemble an adult fly connectome was likely to be won by the FlyEM project at the Janelia Research Campus of the Howard Hughes Medical Institute in Virginia. In 2020, FlyEM researchers led by veteran fly biologist Gerry Rubin published a connectome of an adult fruit-fly “hemibrain”, a set of 27,000 neurons in the middle of the organ. This was followed in 2023 by an assemblage of 3,016 neurons from a first-instar fly larva – a tiny grub emerging from an egg. But Genelia has been appointed to the position by a group called Flywire based at Princeton University to create a whole-brain connectome. Ironically, Flywire used data collected by Genelia, but abandoned it in 2018 after finding it too difficult to analyze with the artificial-intelligence (AI) software available at the time.

However, Flywire’s creators Mala Murthy and Sebastian Seung had different AI software. He started the project in 2018 with support from the BRAIN Initiative (a US government effort to do for neuroscience what the Human Genome Project did for genetics) to analyze Genelia’s now-abandoned data. The result, published in Nature this week, is a model that paints a detailed picture of a female fly’s brain with 139,255 neurons, and traces some 54.5m of synaptic connections between them.

Building a connectome means taking things apart and putting them back together. An electron microscope is used to dissect the brain and record it as a series of slices. Putting it back together uses AI software to trace the multiple projections of neurons in the slice, identify connections and record them.

Genelia researchers had developed two ways to do these things. The FlyEM team used a beam of gallium atoms to destroy nanometer tissue from a brain sample and then recorded an image of each newly exposed surface with a scanning electron microscope (which fires a beam of electrons at the surface). and subsequently detects any radiation emitted). , The male should have his own fruit fly connector, ready within a year.

Janelia’s second method involved shaving layers from the sample with a diamond knife and recording them using a transmission electron microscope (which sends its beam through the target rather than scanning its surface). This is the data used by Flywire. In Genelia’s library of 21 million images, created this way, Dr. Murthy and Dr. Seung, along with 622 researchers from 146 laboratories around the world (plus 15 enthusiastic “citizen scientists” video-gamers, who proofread and annotated the results Helped to do) Helped with the help of. , bet on their software-writing credibility on being able to link images together into a connectome. Which he did.

In addition to the number of neurons and synapses in the fly brain, Flywire researchers also counted the number of types of neurons (8,577) and calculated the combined length (149.2 meters) of the message-carrying axons that connect the cells. Even more importantly, they have enabled us to elucidate not only the connections of a neuron with its nearest neighbors, but also the connections of those neurons with distant regions. In this way a complete study of neural circuitry can be done. Researchers on the project have more than doubled the number of known cell types in the fly’s all-important optic lobe, and shown how the new cell types connect into circuits that deal with different elements of vision, including motion, objects, and colors. .

This kind of thing is scientifically interesting. But to justify the dollars spent on them, projects like FlyEM and Flywire must also serve two practical goals. The aim is to improve the technology of building a connectome, so that it can be used on larger and larger targets – eventually, perhaps including the brains of Homo sapiens. The second is to explore the extent to which non-human brains can serve as models for the human brain (in particular, models that can be experimented on in ways that would be approved by ethics committees). .

Here, evolutionary biology gets involved. Fruit flies and humans are on opposite sides of a 670-year-old divide that divides bilaterally symmetrical animals into two groups: protostomes and deuterostomes. This separation almost certainly predates the evolution of the brain, meaning that the brains of insects (which are protostomes) and the brains of vertebrates (deuterostomes) have different origins. Thus, drawing conclusions about one from the other is risky.

It shouldn’t matter in the long run. Several groups are currently working on mouse connectomes, bits of which have already been put together. Although Genelia has no plans to move in this direction, Dr. Rubin (who, along with several other Genelia researchers, is a co-author of part of a package of nine Nature papers) believes that within a decade a complete Mouse connectome can be created. If someone is willing to spend $1 billion to pay for it. Analogous to the human genome project, where the technology became increasingly cheaper as things progressed, this would also reduce costs to the point where small connectomes like those of flies could be mass produced.

The deuterostome-protostome division, together with recent evolutionary changes, also offers the possibility of a new science of comparative connectomology. In some cases it is already clear that natural selection in cherries has been applied multiple times to multiple solutions to the same problem. For example, the broad organization of neurons in the fly brain and the vertebrate brain is completely different. However, in other instances, both brains seem to work in the same way, which suggests that this may be the best way to do things.

These natural experiments, whose circuit-diagrams connectomes will provide, can also help human computer scientists. After all, brains are quite successful information processors, so reproducing them in silicon might be a good idea. Since it is AI models that have made connectomics possible, it would be poetic if connectomics could, in turn, help develop better AI models.