The Triple Helix @ UChicago

Spring 2014

"A New Lens: Direction selectivity elucidated through novel 'EyeWire' mapping" by Tima Karginov


Direction selectivity of the human retina has recently been supported as a potential mechanism for response to moving visual stimuli. Fifty years after its discovery, direction selectivity may be further explored using a novel space-time wiring technique. In an attempt to model the retina and elucidate direction selectivity, researchers behind the project created an intelligent computer program called “EyeWire” and invited gamers to challenge their own neuronal connections. 

The central mechanism behind direction selectivity is the release of neurotransmitters by excitatory and inhibitory interneurons – integral parts of the nervous system that join neural networks together. The neurotransmitters move through the ganglion cell – a neuron on the inner surface of the retina that receives visual information from photoreceptors through bipolar cells (BC) – and rapidly creates a direction preference for bright and dark moving objects. Direction selectivity, then, is a response of the retina to a stimulus and a “choice” to follow the stimulus.[1] 

Direction-selective ganglion cells (DS cells) form crucial contact with starburst amacrine cells (SACs) and BCs in order to follow their preferred stimulus. SACs are activated by a motion outward from the cell body to the tip of the dendrite – SAC’s namesake branches, which “burst” off of the center cell and respond to electrochemical stimuli. Bipolar Cells, on the other hand, are classified into different types based on the time it takes for them to react to a visual stimulus. SACs are linked to their corresponding BC cells and react by direction selectivity based on where the motion occurred. Essentially, the SAC-BC circuit is dependent on the spatiotemporal phenomenon of motion – the idea that an object in one area will be in another area after a time gap. DS ganglion cells are thus part of a space-time wiring complex required for direction specificity in the retina.[2] 

In order to elucidate the theory of space-time wiring, researchers needed to initially map out a wide array of DS cells and SACs. To do so, Dr. Sebastian Seung and collaborators took on a massive project using mouse retinal images and advanced programming. Seung’s group created EyeWire: A video game designed to color code serial block-face scanning electron microscopy (SBEM) images of three-dimensional neurons. To recreate the neuronal structure, the researchers used an existing data set of BC-SAC circuitry from the mouse images and grouped images into “voxels” –pixel-like images with a volume in three-dimensional space. The group then opened the game to online “citizen scientists,” enabling users to construct neuronal networks. EyeWire is now accessible to any user with Internet and has over 120,000 subscribers since its launch in December of 2012.[3,4] 

The goal of each player is to color images near a pre-determined location of a neuronal part or search for a new location of a neuronal piece to color. In order to do so, users click into a 2D slice while a 3D rendering is presented nearby. I gave the game a shot and found it rather puzzling; the interface is repetitive and it is not always clear why a certain piece goes in the indicated place. I managed to complete 50 cubes over several weeks and the game became more challenging and intriguing as I joined neuronal chains. EyeWire resembles an endless jigsaw puzzle with points awarded for each successfully completed neuron. The scientific function behind the game seems straightforward. According to the EyeWire group, it takes a professional researcher nearly 50 hours to map out a full neuron and given that there are approximately 81 billion such cells found in the human brain, traditional techniques prove ineffective for mapping the brain as a whole. The players’ efforts, therefore, play a crucial role in expediting neuronal mapping. 

Recently, the Seung group expanded upon their original efforts with the “Starburst Challenge.” The key innovation of this trial was to allow users to partake in a test for the hypothesis of direction selectivity. Rather than merely color-coding regular neurons, users were now able to trace a wide variety of cells in the retina. These new types of cells included SACs, BCs, photoreceptors, and ganglion cells. Using new neuronal maps from the Starburst Challenge, researchers were able to identify arranged patterns of the various cells. The BC2 cell, for instance, was found to be near the center of SACs and contained a time lag when responding to a stimulus. BC3a cells, on the other hand, were found to be further out on the dendrites of SACs and, along with the BC2, were known to fire off signals to the ganglion cell. The more powerful dendrite (with the stronger signal) then determines the direction and exhibits directional selectivity.[3,4] 

Although direction selectivity is likely not the only mechanism behind retinal function, the Seung group was able to use a novel, crowdsource method to support an age-old hypothesis. EyeWire technology represents a possibility for further exploration of human networks, ranging from the olfactory bulb to the ear. As a result of their efforts, over 2000 of the EyeWire enthusiasts were noted for their efforts through a co-authorship with the Seung group on their most recent Nature publication.

Check out EyeWire for yourself at


[1] B. Sivyer and S. Williams. 2013. “Direction selectivity is computed by active dendritic integration in retinal ganglion cells.” Nature Neuroscience. 16, 1848-1856. Accessed May 1, 2014. doi:10.1038/nn.3565
[2] D. Vaney, B. Sivyer, W. Taylor. 2012. “Direction selectivity in the retina: symmetry and assymetry in structure and function.” Nature Neuroscience. 13.3, 194-208. Accessed May 1, 2014.doi:10.1038/nrn3165
[3] H.S. Seung et. al and the EyeWirers. 2014. “Space-time wiring specificity supports direction selectivity in the retina.” Nature.509, 7500. 331-336. Accessed May 1, 2014. doi: 10.1038/nature13240
[4] A. Boyle. 2014. “EyeWire Video Gamers Help Untangle Retina’s Space-Time Secrets.” NBC News. Accessed May 1, 2014. 

UChicago Triple Helix