On-Off Direction-Selective Ganglion Cell



Direction selective (DS) cells in the retina are neurons that respond differentially to the direction of a visual stimulus. The term is used to describe a group of neurons that preferrentially "gives a vigorous discharge of impulses when a stimulus is moved through its receptive field in one direction". There are three known types of DS cells in the vertebrate retina of the mouse, ON/OFF DS ganglion cells, ON DS Ganglion Cells (which respond to the leading edge of a bright stimulus) and OFF DS Ganglion Cells (which respond only to the trailing edge of a bright stimulus). Each has a distinctive physiology and anatomy. The rest of this page will only apply to ON/OFF DS Ganglion Cells.

Physiology
ON/OFF DSGCs act as local motion detectors. If a bright stimulus (e.g., a light) is moving in the direction of the cell's preference, the cell will fire at both the leading and trailing edge. An important contrast is that bright stimuli moving opposite the preferred direction (called the null direction), elicit little or no response. The response to stimulus is independent of many stimulus properties, including size, shape, color, and speed. These cells have a center-surround structure, and the size of the dendrite correlates with the size of the center receptive field.

ON/OFF DSGCs can be divided into 4 subtypes differing in their directional preference, ventral, dorsal, nasal, or temporal. The cells of different subtypes also differ in their dendritic structure and synaptic targets in the brain.

From the early experiments in the 1960s, it was shown that receptive fields are fairly large, sensitive to small changes, and direction-selective subunits are repeated many times throughout the retina.



Anatomy
The ON/OFF DSGCs are commonly recognized by their bistratified dendritic arbors, which extend to two layers of the inner plexiform layer (IPL). These cell types are also known to synapse with both bipolar and starburst amacrine cells (SAC). As described above, there are four cell subtypes, each with own preference for direction. Each subtype of ON/OFF DSGCs has differences in dendritic patterns and axonal projections to the brain. These differences indicate that outputs from different subtypes may wire to different parts of the brain.



Connections
Excitation comes from both bipolar cells and starburst amacrine cells. The main source of inhibition is from Starburst Amacrine Cells. Using manual reconstruction of 6 ON/OFF DSGCs and their synaptic partners, it was found that over 90% of SAC – ON/OFF DSGC synapses were oriented in the null direction. An example of the connections found between DSGCs and SACs is shown in the figure below.

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As illustrated in the accompanying figure, light enters the retina through the photoreceptors, and excitatory inputs are transmitted to the ON/OFF DSGCs via Glutamate and Acetylcholine from the bipolar and starburst amacrine cells. Inhibitory GABA inputs, which are crucial for suppressing information in the null direction (and thereby creating a direction-selective motion detector) are received from SACs. The motion detection result is fed to higher parts of the brain for further processing.



Molecules
As described above, ON/OFF DS ganglion cells can be divided into 4 subtypes differing in their directional preference, ventral, dorsal, nasal, or temporal. Recent research has identified markers for distinguishing between the different subtypes, and for separating ON/OFF DSGCs from other retinal ganglion cells. These markers are independent of experience, and suggest a method for how these cells obtain different inputs. Recent research has lead to the development of transgenic mouse lines that selectively mark ON/OFF DSGCs that prefer ventral or nasal motion and another line that marks ventral and dorsal preferring DSGCs. These lines were used to identify cell surface molecules (including Cadherin 6, CollagenXXV1, and Matrix metalloprotease 17), that allow each of the four types of ON/OFF DSGCs to be differentiated. A neuropeptide, CART (cocaine and amphetamine regulated transcript) has been found to differentiate ON/OFF DSGCs from all other retinal ganglion cells. Strikingly, these patterns of molecular differentiation occur before animal eye-opening, and demonstrate that these differences are experience-independent. Therefore, the molecular differences may help to explain the differing functionality between subtypes.



Models
The firing pattern of On-Off Direction-Selective Ganglion cells is time-dependent and is supported by the Reichardt- Hassenstain model, which detects spatiotemporal correlation between two adjacent cells.



As applied to the visual system, this model considers the processed stimulus(i.e., light) inputs to two adjacent cells. After a time delay, each delayed input is multiplied by the original signal from the other cell. The resulting signals are subtracted, and the positive outcome indicates the preferred direction.

This behavior was validated in the visual system using calcium imaging in the fly. However, this model correspondence has only been completed at a high-level (input-output), rather than at an anatomical or physiological level (Borst, Alexander, and Thomas Euler. “Seeing Things in Motion: Models, Circuits, and Mechanisms.” Neuron 71.6 (2011) : 974-994.).

History
Direction Selective units were first explored in cats by Hubel and Wiesel in 1959. Levick and Barlow performed many of the seminal early experiments related to direction selectivity during the 1960s using rabbit retina. In these experiments, they measured action potentials generated from a black-white grating with a small slit. Many additional experiments have been performed during the past fifty years in organisms as diverse as the turtle (e.g., Marchiafava 1979) and the mouse (Briggman 2011).

Open questions / status / relevance to eyewire
Cells will be available for tracing in Eyewire, although these cells are not currently available (March 2012). See http://wiki.eyewire.org/wiki/E2198

Reading List
K. L. Briggman, M. Helmstaedter, and W. Denk, Wiring specificity in the direction-selectivity circuit of the retina., Nature, vol. 471, no. 7337, pp. 183-8, Mar. 2011.

A. Borst and T. Euler, Review Seeing Things in Motion : Models, Circuits and Mechanisms, Neuron, vol. 71, no. 6, pp. 974-994, 2011.

D. I. Vaney, B. Sivyer, and W. R. Taylor, Direction selectivity in the retina: symmetry and asymmetry in structure and function, Nature Reviews Neuroscience, vol. 13, no. 3, pp. 194-208, Jan. 2012.

W. R. Levick and H. B. Barlow, The Mechanism of Directionally Selective Units in Rabbit's Retina, pp. 477-504, 1965.