Researchers crowdsource brain mapping with gamers, discover six new neuron types

May 17, 2018, Princeton University
By turning a time-intensive research problem into an interactive game, Princeton neuroscientist Sebastian Seung has built an unprecedented data set of neurons, which he is now turning over to the public via the Eyewire Museum. These 17 retinal neurons, mapped by Eyewire gamers, include ganglion cell types in blue and green and amacrine cells in yellow and red. Credit: Alex Norton, Eyewire

With the help of a quarter-million video game players, Princeton researchers have created and shared detailed maps of more than 1,000 neurons—and they're just getting started.

"Working with Eyewirers around the world, we've made a digital museum that shows off the intricate beauty of the 's neural circuits," said Sebastian Seung, the Evnin Professor in Neuroscience and a professor of computer science and the Princeton Neuroscience Institute (PNI). The related paper is publishing May 17 in the journal Cell.

Seung is unveiling the Eyewire Museum, an interactive archive of neurons available to the general public and neuroscientists around the world, including the hundreds of researchers involved in the federal Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative.

"This interactive viewer is a huge asset for these larger collaborations, especially among people who are not physically in the same lab," said Amy Robinson Sterling, a crowdsourcing specialist with PNI and the executive director of Eyewire, the online gaming platform for the citizen scientists who have created this data set.

"This museum is something like a brain atlas," said Alexander Bae, a graduate student in electrical engineering and one of four co-first authors on the paper. "Previous brain atlases didn't have a function where you could visualize by individual cell, or a subset of cells, and interact with them. Another novelty: Not only do we have the morphology of each cell, but we also have the functional data, too."

The neural maps were developed by Eyewirers, members of an online community of video game players who have devoted hundreds of thousands of hours to painstakingly piecing together these , using data from a mouse retina gathered in 2009.

Eyewire pairs machine learning with gamers who trace the twisting and branching paths of each neuron. Humans are better at visually identifying the patterns of neurons, so every player's moves are recorded and checked against each other by advanced players and Eyewire staffers, as well as by software that is improving its own pattern recognition skills.

Since Eyewire's launch in 2012, more than 265,000 people have signed onto the game, and they've collectively colored in more than 10 million 3-D "cubes," resulting in the mapping of more than 3,000 neural cells, of which about a thousand are displayed in the museum.

By turning a time-intensive research problem into an interactive game, Princeton neuroscientist Sebastian Seung has built an unprecedented data set of neurons, which he is now turning over to the public via the Eyewire Museum. Eyewire gamers mapped this synapse between a ganglion neuron (blue) and a starburst amacrine cell (yellow). Credit: Alex Norton, Eyewire

Each cube is a tiny subset of a single cell, about 4.5 microns across, so a 10-by-10 block of cubes would be the width of a human hair. Every cell is reviewed by between 5 and 25 gamers before it is accepted into the system as complete.

"Back in the early years it took weeks to finish a single cell," said Sterling. "Now players complete multiple neurons per day." The Eyewire user experience stays focused on the larger mission—"For science!" is a common refrain—but it also replicates a typical gaming environment, with achievement badges, a chat feature to connect with other players and technical support, and the ability to unlock privileges with increasing skill. "Our top players are online all the time—easily 30 hours a week," Sterling said.

Dedicated Eyewirers have also contributed in other ways, including donating the swag that gamers win during competitions and writing program extensions "to make game play more efficient and more fun," said Sterling, including profile histories, maps of player activity, a top 100 leaderboard and ever-increasing levels of customizability.

"The community has really been the driving force behind why Eyewire has been successful," Sterling said. "You come in, and you're not alone. Right now, there are 43 people online. Some of them will be admins from Boston or Princeton, but most are just playing—now it's 46."

For science!

With 100 billion neurons linked together via trillions of connections, the brain is immeasurably complex, and neuroscientists are still assembling its "parts list," said Nicholas Turner, a graduate student in computer science and another of the co-first authors. "If you know what parts make up the machine you're trying to break apart, you're set to figure out how it all works," he said.

The researchers have started by tackling Eyewire-mapped ganglion cells from the retina of a mouse. "The retina doesn't just sense light," Seung said. "Neural circuits in the retina perform the first steps of visual perception."

The retina grows from the same embryonic tissue as the brain, and while much simpler than the brain, it is still surprisingly complex, Turner said. "Hammering out these details is a really valuable effort," he said, "showing the depth and complexity that exists in circuits that we naively believe are simple."

The researchers' fundamental question is identifying exactly how the retina works, said Bae. "In our case, we focus on the structural morphology of the ."

"Why the ganglion cells of the eye?" asked Shang Mu, an associate research scholar in PNI and fellow first author. "Because they're the connection between the retina and the brain. They're the only cell class that go back into the brain." Different types of ganglion cells are known to compute different types of visual features, which is one reason the museum has linked shape to functional data.

Using Eyewire-produced maps of 396 , the researchers in Seung's lab successfully classified these cells more thoroughly than has ever been done before.

"The number of different cell types was a surprise," said Mu. "Just a few years ago, people thought there were only 15 to 20 ganglion cell types, but we found more than 35—we estimate between 35 and 50 types."

Of those, six appear to be novel, in that the researchers could not find any matching descriptions in a literature search.

A brief scroll through the digital museum reveals just how remarkably flat the neurons are—nearly all of the branching takes place along a two-dimensional plane. Seung's team discovered that different grow along different planes, with some reaching high above the nucleus before branching out, while others spread out close to the nucleus. Their resulting diagrams resemble a rainforest, with ground cover, an understory, a canopy and an emergent layer overtopping the rest.

All of these are subdivisions of the inner plexiform layer, one of the five previously recognized layers of the retina. The researchers also identified a "density conservation principle" that they used to distinguish types of neurons.

One of the biggest surprises of the research project has been the extraordinary richness of the original sample, said Seung. "There's a little sliver of a mouse retina, and almost 10 years later, we're still learning things from it."

Explore further: New insights into how the retina processes orientation

More information: J. Alexander Bae et al, Digital Museum of Retinal Ganglion Cells with Dense Anatomy and Physiology, Cell (2018). DOI: 10.1016/j.cell.2018.04.040

Related Stories

New insights into how the retina processes orientation

February 26, 2018
In a study published in Nature Communications, Northwestern Medicine scientists detail the discovery of two types of cells in the retina that determine horizontal or vertical orientation, and demonstrated for the first time ...

Making connections in the eye: Wiring diagram of retinal neurons is first step toward mapping the human brain

August 7, 2013
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 ...

EyeWire gamers help researchers understand retina's motion detection wiring

May 5, 2014
(Medical Xpress)—A team of researchers working at MIT has used data supplied by gamers on EyeWire to help explain how it is that the retina is able to process motion detection. In their paper published in the journal Nature, ...

Researchers shed light on how our eyes process visual cues

June 7, 2017
The mystery of how human eyes compute the direction of moving light has been made clearer by scientists at The University of Queensland.

New technique classifies retinal neurons into 15 categories, including some previously unknown types

March 24, 2014
As we scan a scene, many types of neurons in our retinas interact to analyze different aspects of what we see and form a cohesive image. Each type is specialized to respond to a particular variety of visual input—for example, ...

Overlooked cell key player in preventing age-related vision loss

March 6, 2018
Duke researchers have pinpointed a new therapeutic target for macular degeneration, an eye disease that affects over 10 million Americans and is the leading cause of blindness in adults over 60.

Recommended for you

Environmental factors may trigger onset of multiple sclerosis

October 16, 2018
A new Tel Aviv University study finds that certain environmental conditions may precipitate structural changes that take place in myelin sheaths in the onset of multiple sclerosis (MS). Myelin sheaths are the "insulating ...

Study points to possible new therapy for hearing loss

October 15, 2018
Researchers have taken an important step toward what may become a new approach to restore hearing loss. In a new study, out today in the European Journal of Neuroscience, scientists have been able to regrow the sensory hair ...

Scientists examine how neuropathic pain responds to Metformin

October 15, 2018
Scientists seeking an effective treatment for one type of chronic pain believe a ubiquitous, generic diabetes medication might solve both the discomfort and the mental deficits that go with the pain.

Sugar, a 'sweet' tool to understand brain injuries

October 15, 2018
Australian researchers have developed ground-breaking new technology which could prove crucial in treating brain injuries and have multiple other applications, including testing the success of cancer therapies.

Abnormal vision in childhood can affect brain functions

October 13, 2018
A research team has discovered that abnormal vision in childhood can affect the development of higher-level brain areas responsible for things such as attention.

Study: Ketogenic diet appears to prevent cognitive decline in mice

October 12, 2018
We've all experienced a "gut feeling"—when we know deep down inside that something is true. That phenomenon and others (like "butterflies in the stomach") aptly describe what scientists have now demonstrated: that the gut ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

dan78658765
not rated yet May 19, 2018
gamers have two dimensional neurons.. not a surprise

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.