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Snapshots of Life: A Colorful Look Inside the Retina

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Mapping neurons in the retina

Credit: Amy Robinson, Alex Norton, William Silversmith, Jinseop Kim, Kisuk Lee, Aleks Zlasteski, Matt Green, Matthew Balkam, Rachel Prentki, Marissa Sorek, Celia David, Devon Jones, and Doug Bland, Massachusetts Institute of Technology, Cambridge, MA; Sebastian Seung, Princeton University, Princeton, NJ

This eerie scene might bring back memories of the computer-generated alien war machines from Steven Spielberg’s War of the Worlds thriller. But what you’re seeing is a computer-generated depiction of a quite different world—the world inside the retina, the light-sensitive tissue that lines the back of the eye. The stilt-legged “creatures” are actually ganglion nerve cells, and what appears to be their long “noses” are fibers that will eventually converge to form the optic nerve that relays visual signals to the brain. The dense, multi-colored mat near the bottom of the image is a region where the ganglia and other types of retinal cells interact to convey visual information.

What I find particularly interesting about this image is that it was produced through the joint efforts of people who played EyeWire, an internet crowdsourcing game developed in the lab of computational neuroscientist Sebastian Seung, now at Princeton University in New Jersey.  Seung and his colleagues created EyeWire using a series of high-resolution microscopic images of the mouse retina, which were digitized into 3D cubes containing dense skeins of branching nerve fibers. It’s at this point where the crowdsourcing came in. Online gamers—most of whom aren’t scientists— volunteered for a challenge that involved mapping the 3D structure of individual nerve cells within these 3D cubes. Players literally colored-in the interiors of the cells and progressively traced their long extensions across the image to distinguish them from their neighbors. Sounds easy, but the branches are exceedingly thin and difficult to follow.

Snapshots of Life: Lost Connections in Pompe Disease

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Junctions between motor neurons (green) and muscle fibers (red)

Caption: Abnormal connections between leg muscle fibers (red) and nerves (green) in Pompe disease.
Credit: Darin J. Falk, A. Gary Todd, Robin Yoon, and Barry J. Byrne, University of Florida, Gainesville

Mistletoe? Holly? Not exactly. This seemingly festive image is a micrograph of nerve cells (green) and nerve-muscle junctions (red) in a mouse model of Pompe disease. Such images are helping researchers learn more about this rare form of muscular dystrophy, providing valuable clues in the ongoing search for better treatments and cures.

People with Pompe disease lack an enzyme that cells depend on to break down a stored sugar, known as glycogen, into smaller glucose molecules that can be readily used for energy. Without enough of this enzyme, called acid alpha-glucosidase (GAA), glycogen can accumulate destructively in the liver, heart, and skeletal muscles, making it increasingly difficult to walk, eat, and even breathe.

Snapshots of Life: Tracing the Fibers of Addiction

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DTI fiber tracking image

Credit: John D. Olson, Paul W. Czoty Michelle Bell, Wake Forest School of Medicine, Winston-Salem, NC

This may look like a light-hearted piece of string art, but it’s actually part of a very serious effort to understand what happens to the brain when it’s strung out on drugs. The image, one of the winners of the Federation of American Societies for Experimental Biology’s 2013 BioArt competition, was created with an advanced form of magnetic resonance imaging called Diffusion Tensor Imaging (DTI).

DTI works by detecting the movement of water in the nerve cells of a living brain. By determining which direction water is flowing in axons, the long processes that convey signals to other neurons, researchers can figure out whether the neurons are stretching from the left to right side of the brain (red), top to bottom (blue), or front to back (green). This data is then used to construct a three-dimensional view of the brain and its connections.

Snapshots of Life: Fisheye View

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Goldfish retina

Credit: Bryan William Jones and Robert E. Marc, University of Utah, Salt Lake City

It looks like a celebration with confetti and streamers that the photographers—among the winners of the Federation of American Societies for Experimental Biology’s 2013 BioArt Competition—captured in this image. But these dots and lines are actually cells in the retina of a goldfish. And what such images reveal may be far more than just a pretty picture.

NIH-funded researchers at the University of Utah used a set of tools called Computational Molecular Phenotyping (CMP) to take a snapshot of the amacrine cells in the retina. The retina is delicate, light-sensitive tissue in the back of the eye, and its amacrine cells are involved in processing and conveying signals from the light-gathering photoreceptor cells to the brain’s visual cortex, where the image is decoded. The colors in this photograph reveal the unique metabolic chemistry, and thus the identity, of each subtype of neuron. The red, yellow, and orange cells are amacrine neurons with a high level of the amino acid glycine; the blue ones have a lot of the neurotransmitter gamma-aminobutyric acid (GABA). The green color tells us something different: it provides a physiological snapshot revealing which neurons were active and talking to each other at the time the image was created.

Snapshots of Life: Reward Seeking, in Technicolor

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Rainbow noodles

Credit: Saleem Nicola, Vincent B. McGinty, James J. Kim, and Sylvie Lardeux

Originally, this vibrant picture was just a set of black lines on a graph, charting the various paths of a laboratory rat as it made its way toward a lever to release a shot of sugar water. But Dr. Saleem Nicola, an NIH-funded researcher at Albert Einstein College of Medicine, Bronx, NY, wanted to pique the interest of his colleagues, so he decided to have a bit of fun with the image.

First, Dr. Nicola broadened the lines, giving them a noodle-like appearance. He then went on to use other information about the rat journeys to add rainbow hues, and, finally, he replaced the white background with black. The result is an eye-catching image that is among the winners of the Federation of American Societies for Experimental Biology’s 2013 BioArt competition.

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