Scientists have created the first complete map of the tiny insect’s brain, including all its neurons and connecting synapses. The research, published March 9 in Science1, provides for the first time a brain wiring diagram known as the connectome of a complex animal — the fruit fly Drosophila melanogaster. The map shows all 3,016 neurons and 548,000 synapses tightly packed in the brain of a young Drosophila, which is smaller than a poppy seed.
The map is a milestone in understanding how the brain processes the flow of sensory information and translates it into action. “We now have a reference brain,” says Marta Zlatic, a neuroscientist at the University of Cambridge in the UK and co-author of the paper. “We can look at what happens to connectivity in models of Alzheimer’s and Parkinson’s and any degenerative disease.”
The ideal model
Until now, scientists have only mapped the connectomes of the worms Caenorhabditis elegans and Platynereis dumerilii and the larvae of the sea squirt Ciona intestinalis. Drosophila was an ideal model for studying connectomes because scientists had already sequenced its genome and larvae have transparent bodies.
Fruit flies also exhibit sophisticated behaviors—including learning, navigating the landscape, processing odors, and weighing the risks and benefits of action. “Its size is manageable for current technology,” says Chung-Chuang Lo, a computational neuroscientist at National Tsing Hua University in Hsinchu, Taiwan.
“If you had asked me about this fruit fly project in the 1980s when I was working on C. elegans, it would have been impossible,” says Albert Cardona, a neuroscientist at the University of Cambridge and a co-author.
Scientists spent a year and a half taking images of the brain of a single six-hour-old Drosophila larva using an electron microscope with nanometer resolution. They then pinpointed the neurons and synapses using a computer-aided program and spent months inspecting them manually.
The authors identified 3,016 neurons, of which 93% were paired with a partner neuron in the opposite cerebral hemisphere. Most of the unpaired neurons were Kenyon cells, key neurons at the center of learning and memory.
The researchers then traced the twisted connections of each neuron and identified 548,000 synapses that could be grouped into four types. “It’s really time-consuming and labor-intensive,” says Kei Ito, a neuroscientist at the University of Cologne in Germany.
Most work on connectomes has involved one type of connection—from the axon of one neuron to the dendrites of another—and has ignored axon-axon or dendrite-dendrite connections. “Now we have to rethink them: we will probably have to think about creating a new computational model of the nervous system,” says Lo.
The wiring diagram showed that the insect’s brain was multi-layered, with pathways of various lengths connecting brain inputs and brain outputs.
It’s a “nice, nested structure,” says Michael Winding, a neuroscientist at the University of Cambridge and co-author of the paper. But some brain networks have shortcuts, skipping layers. The authors suggest that such shortcuts increase the brain’s computational capacity and compensate for the limited number of neurons.
The team also found that 41% of the brain’s neurons form “recurrent loops” that provide feedback to their upstream partners. These shortcuts and loops resemble the state-of-the-art artificial neural networks used in artificial intelligence research. “It’s interesting that the field of computer science is converging on what evolution has discovered,” says Cardona.
The current map provides data from a single animal, but the authors say technological advances will allow more flies — and possibly other species — to be mapped. “Now it can be used to train machine learning to make it much faster,” says Zlatic.
“It’s not the whole story,” says Lo. The next step is to map the adult Drosophila brain, which is more complex and has more neurons, he adds.
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