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The most advanced brain map to date, that of an insect, brings scientists closer to truly understanding the mechanism of thought.
Researchers have created a stunningly detailed diagram that traces every neural connection in the brain of a larval fly, an archetypal scientific model with brains comparable to humans.
The work, which will likely underpin future brain research and inspire new machine learning architectures, appears in the journal Science.
“Everything has worked up to this point.”
“If we want to understand who we are and how we think, part of that is understanding the mechanism of thought,” says senior author Joshua T. Vogelstein, a biomedical engineer at Johns Hopkins University who specializes in data-driven projects including connectomics. the study of the connections of the nervous system. “And the key to that is knowing how neurons connect to each other.”
The first attempt to map a brain—a 14-year study of the roundworm that began in the 1970s resulted in a partial map and a Nobel Prize. Since then, some connections have been mapped in many systems, including flies, mice, and even humans, but these reconstructions typically represent only a tiny fraction of the total brain.
Complete connections have been established only for several small species with a few hundred to a few thousand neurons in their body: a roundworm, a larval sea squirt, and a larval sea worm.
The link of this group of a fruit fly, Drosophila melanogaster larva, is the most complete as well as the most extensive map of an entire insect brain ever completed. It includes 3,016 neurons and each connection between them: 548,000.
“It’s been 50 years and this is the first brain connection. It’s a flag in the sand that we can do this,” Vogelstein says. “Everything has worked up to this point.”
Map of brain connections
Mapping whole brains is difficult and extremely time-consuming, even with the best modern technology. Getting a complete picture of a brain at the cellular level requires slicing the brain into hundreds or thousands of individual tissue samples, which must be imaged with electron microscopes before the painstaking process of reconstructing all those pieces, neuron by neuron, into complete, accurate portrait of a brain.
It took over a decade to do this with the fruit fly. The brain of a mouse is estimated to be a million times larger than that of a fruit fly, meaning that the possibility of mapping anything close to a human brain is unlikely in the near future, perhaps even in our lifetime.
The team deliberately chose the 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 12 years from the University of Cambridge and Johns Hopkins. Imaging alone took about a day per neuron.
The Cambridge researchers created the high-resolution images of the brain and pored over them manually to find individual neurons, rigorously locating each one and connecting their synaptic connections.
Cambridge delivered the data to Johns Hopkins, where the team spent more than three years using the original code they created to analyze brain connectivity. The Johns Hopkins team developed techniques to find groups of neurons based on shared patterns of connectivity and then analyzed how information might propagate through the brain.
In the end, the full team mapped every neuron and every connection, and categorized each neuron based on the role it plays in the brain. They found that the busiest brain circuits were those leading to and away from learning center neurons.
Brain comparisons
The methods the researchers developed are applicable to any brain-wiring project, and their code is available to anyone attempting to map an even larger animal brain, Vogelstein says, adding that despite the challenges, scientists are expected to tackle the mouse, possibly within the next decade.
Other groups are already working on a map of the adult 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 adult and larval brains. As links are made to more larvae and other related species, Pedigo expects their analysis techniques could lead to a better understanding of variations in brain wiring.
Work with fruit fly larvae showed circuit characteristics strikingly reminiscent of prominent and powerful machine learning architectures. The team expects that continued study will reveal even more computational principles and potentially inspire new artificial intelligence systems.
“What we learned about the code for fruit flies will have implications for the code for humans,” says Vogelstein. “That’s what we want to figure out—how to write a program that drives a human brain network.”
Source: Johns Hopkins University
