First Complete Map of a Fly Brain Has Uncanny Similarities to AI Neural Networks

Researchers spent 12 years mapping a fruit fly larva's entire brain, cataloging 3,016 neurons and 548,000 synapses. For neurobiology, it's major news.

A fruit fly pup appears to the majority of people to be a small, rice grain-shaped, pale, and writhing maggot. However, fly embryos also have complex and fascinating lives that are full of sense information, social interactions, and learning. Now that we have the chart, there is no longer any question that there is a lot going on inside a maggot's brain.

A thorough reconstruction and study of a larval fruit fly's brain have been published by a multidisciplinary team of researchers on Thursday in the journal Science. The 3,016 neurons and 548,000 synapses that make up the baby fly's central nervous system are all represented in the final image, or connectome, as it is known in neurobiology. The nerve cord and both of the larva's cerebral regions are part of the connectome.

A nematode (C. elegans) provided the first (almost) entirely full connectome, which was released in 1986. Those scientists had to hand-draw links using colored pencils to create the original plan. 7,600 synapses and other links, along with 302 neurons, were involved.

Since then, a branch of neuroscience has emerged with the goal of mapping the minds of ever-more-complex creatures. And significant advancements have already been made. We have obtained completely accurate images of several worm brains. 2018 saw the publication of a brain map of a mature fruit fly that was comparatively low-resolution and lacked comprehensive connective analysis.

A partial connectome of a mature fruit fly's central brain was released in 2020 by a multi-institute team that included researchers from Google and the Janelia Campus of the Howard Hughes Medical Institute (25,000 neurons, 20 million connections). A follow-up study of that portion of the adult fly brain was released by a related Janelia research team a year later, and it started to explain the "why and how" behind the "what." The researchers in that study from 2021 outlined sensory and motor networks as well as other intricate processes that help explain how a fly's brain gives it the ability to be a fly.

But this is the first time that a complete insect brain has been imaged and studied at such a high density by experts. It is the most comprehensive cerebral map of an insect ever created and the most complex documented connectome of any mammal. In a nutshell, it changes the game.

It may signal a paradigm change in the study of neurobiology for some. Since fruit flies are model animals, it is believed that many neural structures and pathways have been preserved throughout development. What holds true for maggots may also hold true for rodents, other animals, or even people. According to several scientists who spoke with Gizmodo, researchers will use this brain as a guide in their research across subfields, much like how biologists used the first human genome map. We now have more knowledge than ever before about the nervous system, neural networks, and cerebral architecture of a species. Additionally, study in areas other than neuroscience, such as artificial intelligence and developmental biology, could benefit from the recently released connectome.

"I never imagined anything would appear that way."

In an interview with Gizmodo, Timothy Mosca, a neuroscientist researching fruit fly sensory systems at Thomas Jefferson University who was not involved in the new research, said, "It is a tour de force of how we comprehend the ways in which minds are linked.

Some of the basic components of the mammalian brain have been roughly outlined for many years. According to Mosca, researchers were aware of the basic locations of the muscular and sensory neurons. The transition from a hazy satellite view to a clear city street plan, however, is made by this novel connectome. Mosca stated that "now we know where every 7-11 and every, you know, Target [store] is" on the block-by-block grid of an insect's brain.

A team of Cambridge University researchers focused on the brain of a single, 6-hour-old female fruit fly pup for 12 years to finish the connectome. The organ is incredibly tiny, measuring about 170 by 160 by 70 micrometers, which puts it in the same order of scale as objects that are too small to be seen with the unaided eye. However, the scientists were able to visibly divide it into thousands of slices that were only a few nanometers thick using electron imaging. On average, it took a day to image one cell. The study started after the physical image of the neurons, or "brain volume," was finished.

The Cambridge neuroscientists evaluated and classified the neurons and synapses they had discovered with the assistance of computer scientists from Johns Hopkins University. Based on earlier neuroscience studies of behavior and sensory systems, the JHU researchers developed a computer software specifically for this purpose to identify cell and synapse kinds, trends within the brain connections, and to map some function onto the larva connectome.

Many mysteries were discovered. One of the study's lead researchers, Cambridge University neuroscientist Michael Winding, discussed the study's findings in a video call. "The larval fly connectome showed numerous neural pathways that zigzagged between hemispheres, demonstrating just how integrated both sides of the brain are and how nuanced signal processing can be," he said. Winding remarked, "I never imagined anything would appear like that.

Another Cambridge neurobiologist and one of the study's senior researchers, Marta Zlatic, explained in a video call that some areas of the brain had synapses that were highly recursive, repetitive, and reinforced—particularly and "beautifully" in the regions of the brain thought to be responsible for learning.

The design of some artificial intelligence models (referred to as residual neural networks) appears to fascinatingly resemble these recurrent structures mapped from an actual brain, with nested paths allowing for various degrees of intricacy, Zlatic observed. Artificial intelligence (AI) researchers made assumptions about the details of brain anatomy when they developed their artificial proxies of natural information processing. They were right, at least in a limited manner, and now they have more evidence. This description was mirrored by Winding, who referred to the design of the maggot's learning facility as a "Russian doll of connectedness."

The exposed neural structure was stratified, and the neurons themselves seem to have many different faces. Visual, olfactory, and other inputs intersected and engaged with one another as they traveled to the sensory cells' output cells, according to Zlatic. "This brain does a tremendous amount of multi-sensory integration...which is a very potent process computationally," she continued.

Then there were the various kinds and proportions of links between cells. The "canonical" form of synapse in neurobiology connects an axon to a dendrite. However, that only accounted for about two-thirds of the links in the traced larval fly brain, according to Winding and Zlatic. Dendrites linked to dendrites, axons connected to axons, and dendrites linked to axons. Although these kinds of links have been known to exist in animal nervous systems, the study's breadth far exceeded their expectations. Considering the variety of these links, Winding concluded that they must be crucial for brain computation. Just how is a mystery to us.

Connectomes cannot tell us everything, as thrilling as this development is for neuroscientists ("I'm so stoked to be doing research right now," Mosca said). According to Mosca, this is "a snapshot of one instant in time in one species. It closes a significant study void for comprehending the differences in animal brain anatomy between the larval and adult fly phases.

The functions of individual neurons and synapses, as well as how minds evolve over time and vary between people, cannot be determined from a single, distinct image of a fly's neurons and synapses. For example, we don't yet have the information to evaluate male and female fly minds. not to monitor a fly's developing neuronal landscape. It would be like staring at "a flipbook with a few pages missing," according to Mosca, to arrange all of the present connectomes in developmental sequence.

Josh Vogelstein, a JHU network scientist and one of the study authors, said in a video call that DNA is a relatively unchanging dataset, decided with the first cell in an organism's growth, despite frequent parallels to the first full human genome map popping up in discussion. In comparison, he claimed that "your connectome changes every second". Additionally, the definitions that Vogelstein and his coworkers used in their study (i.e., how they drew the map) are arbitrary. He explained that while some might proclaim entire brain areas to be nodes, they described neurons as nodes and synapses as edges. "What a connectome is and how it evolves are not uniformly understood."

We now have more knowledge than ever before about the nervous system, neural networks, and cerebral architecture of a species.

More study is essential to separating out all those unanswered questions. Since this new study's beginning more than ten years ago, imaging developments have made it feasible to gather brain volume data much more rapidly. Additionally, future studies can move much more quickly thanks to the computer software created by Vogelstein and Benjamin Pedigo, his PhD student—on the scale of months for data correction and hours for processing, as opposed to years.

Zlatic wants to gather many more larval fly connectomes using this one as a starting point, and then compare them to find functional connections (such as how the minds of faster wigglers vary from those of slower wigglers). Winding is establishing his own lab group where he will start looking for social behavior-related networks in fruit fly brains. He then wishes to experiment with manipulating those circuits to see what occurs.

The brains of bigger creatures are being mapped by others. At Janelia, work on a fruit fly's entire connectome is well under way. Though such research is probably still years and years away from conclusion, some people have ambitions to progress to animal brains as large and complicated as those of mice.

According to Vogelstein, this represents a development in our ability to fully comprehend (and even write) awareness. Although we haven't gotten there yet, this larval connectome suggests a potential scenario in which a sophisticated animal's brain could be reverse-engineered and turned into a computer software. He said, "As far as I know, everyone in the world recognizes or agrees that you need brains for awareness. A neural map by itself "is not adequate" to solve the puzzle of consciousness. He made it plain that, "there's no way we can simulate a conscious brain just by possessing this connectome. Nevertheless, it is a "central and essential component."

Despite not being a connectome scholar, Mosca believes he is prepared to apply the most recent study on larvae to his own work. This is going to really provide us with a ton of outstanding material for us to be able to pose more complex study questions, he said. "The overwhelming quantity of work this will motivate and that this will influence is nearly infinite" across neurology and biology.