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A Very Close Look at the Eye

Diagramming the wiring of retinal neurons is a first step toward mapping the brain.

The human brain has 100 billion neurons, connected to each other in networks that allow us to interpret the world around us, plan for the future, and control our actions and movements. MIT neuroscientist Sebastian Seung wants to map those networks, creating a wiring diagram of the brain that could help scientists learn how we become our unique selves.

mapped arrangement of neurons
Neuroscientists mapped the arrangement of neurons in a section of mouse retina after imaging the tissue with electron microscopy.

Seung and collaborators at MIT and the Max Planck Institute for Medical Research in Germany recently reported their first step toward this goal: using a combination of human and artificial intelligence, they mapped all the wiring connecting 950 neurons within a tiny patch of a mouse retina.
Composed of neurons that process visual information, the retina is technically part of the brain and is a relatively approachable starting point, Seung says. Retinal neurons fall into one of five classes—photoreceptors, horizontal cells, bipolar cells, amacrine cells, and ganglion cells. Each contains many types, classified by shape and by the connections they make with other neurons. “The retina is estimated to contain 50 to 100 types, but they’ve never been exhaustively characterized,” he says. “And their connections are even less well known.”

By mapping all the neurons in this 117-by-80-micrometer patch of retinal tissue, the researchers were able to classify most of the neurons they found. They also identified a type of retinal cell that had not been seen before.

“It’s the complete reconstruction of all the neurons inside this patch. No one’s ever done that before in the mammalian nervous system,” says Seung, a professor of computational neuroscience at the Institute.

The researchers began by taking electron micrographs of the targeted section to make high-resolution 3-D images. To develop a wiring diagram from these images, they first hired about 225 German undergraduates to trace the “skeleton” of each neuron, which took more than 20,000 hours of work over several years.

Next the researchers fed these traced skeletons into a computer algorithm developed in Seung’s lab. The algorithm detects the boundaries between neurons and then fills in each neuron’s body, making it easier for researchers to see where the neurons contact each other.

If human workers filled in the neuron bodies, it would take 10 to 100 times longer than just drawing the skeleton. The only previous complete wiring diagram, which mapped all the connections between the 302 neurons found in the worm Caenorhabditis elegans, was reported in 1986 and required more than a dozen years of tedious labor.

“This speeds up the whole process,” Seung says. “It’s a way of combining human and machine intelligence.”

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