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On-Off DSGC from DRD4-GFP mouse filled with biocytin. White arrow shows the axon, yellow arrows show "looping" arborizations characteristic of mouse DSGCs. Image adapted from Huberman et al., 2009

Cells that express dopamine receptor D4 (DRD4) are a neuronal cell type in the retina. They are a type of On-Off Direction-Selective Ganglion Cell (On-Off DSGC) that prefers posterior motion within the visual field (motion on the retina towards the nasal pole). Like other On-Off DSGC types, DRD4 cells have bistratified dendrites, and receive synaptic input from starburst amacrine cells. Their axons project to the dorsal lateral geniculate nucleus and the superior colliculus.

Molecular definition

These cells are defined by their expression of DRD4 (dopamine receptor D4). They can be visualized in Drd4-GFP BAC transgenic mice, in which GFP is expressed under the control of the Drd4 promoter (Gong et al., 2003). This mouse line expresses GFP prominently in the prefrontal cortex, and also in the ganglion cell layer (GCL) of the retina (Gong et al., 2003, Huberman et al., 2009). Dendrites of GFP-positive cells stratify in two distinct bands in the inner plexiform layer (IPL) of the retina, a pattern known as bistratification (Huberman et al., 2009). The GFP-positive dendrites appear to be costratified with processes of starburst amacrine cells (SACs).

Saggital section of Drd4 BAC transgenic mouse brain revealing high expression of DRD4 in the prefrontal cortex. Image adapted from Gong et al., 2003
GFP positive cells in Drd4-GFP retina with no immunostaining. Scale= 200um, 100um respectively. Image adapted from Huberman et al., 2009


All DRD4-RGC cells are strongly excited by posterior motion within the visual field, or motion toward the nasal pole of the retina. ON and OFF responses are exhibited in response to flashes of a white spot centered on the soma (Huberman et al., 2009). Responses to drifting graftings reveal strong posterior direction tuning that is more narrowly tuned compared to another type of posterior motion preferring DSGC (TRHR-RGC) (Rivlin-Etzion et al., 2011).

Left: Responses to drift gratings of DRD4-RGCs show a strong posterior direction tuning. Black tuning curve shows mean response, colored curves show each repetition. Right: Vector sums of all recorded cells (n=40). Adapted from Rivlin-Etzion et al., 2011.


Dendritic Morphology

DRD4-RGC cells exhibit canonical morphological characteristics of On-Off DSGCs. They are bistratified, costratifying with starburst amacrine cell (SAC) processes. Their dendritic fields are egg-shaped and arbors exhibit "looping" patterns prevalent in mouse On-Off DSGCs (Huberman et al., 2009). Although their dendritic arbors are mostly symmetric, their somas tend to shift slightly away from the center of their dendritic fields, which distinguishes them from another subtype of posterior motion perferring DSGC (TRHR-RGC). The cells form a regular mosaic with a relatively high coverage factor (2.99 on average) (Rivlin-Etzion et al., 2011).

Mosaic of four DRD4-RGCs. Bistratification of dendrites can be seen below. Scale= 100um. Image adapted from Rivlin-Etzion et al., 2011
Left: Schematic of DRD4-RGC and SAC dendrite costratification in IPL sublamina S2 and S4. SAC in red, DRD4-RGCs in green. Right: DRD4-GFP retinas stained for GFP and vAChT. Scale= 100um. Image adapted from Huberman et al., 2009

Retinal Input

Although the exact cell types that DRD4-RGCs receive input from are still unknown, they are thought to exhibit the same overall connectivity as canonical DSGCs.

Central Projections

DRD4-RGCs send their axons to two retinorecipient areas of the brain: the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus (SC). For both areas, axon terminations are restricted to specific laminae. In the dLGN, DRD4-RGC axons are limited to a lamina running along the lateral dLGN, while in the SC, axons terminate in the upper half of the stratum griseum superficialis (uSGS) (Huberman et al., 2009). Inputs to both dLGN and SC arise from the controlateral eye.

DRD4-RGC axons terminate in a clear laminar distribution throughout the lateral dLGN. Left: The dLGN with merged CTb-594 injected from both eyes (red) and GFP positive cells (green). Dashed line= lateral dLGN, solid line= medial dLGN. Center: CTb-594 only. Right: GFP only. Image adapted from Huberman et al., 2009.
DRD4-RGC axons terminate in a clear laminar distribution throughout the upper stratum griseum superficialis (uSGS). Brackets distinguish uSGS and iSGS (inner SGS). Left: Merge of Ctb-594 positive axons (red) and GFP positive axons (green). Right: GFP positive axons only. Image adapted from Huberman et al., 2009

Behavioral Output

It is difficult at this stage to infer what information these On-Off DSGCs are contributing to in object motion detection. However, the highly specific nature of their central projections reveals several important truths about how DSGCs are computing object motion. Their axons target exclusively the dLGN and SC, with no terminations in any other retinorecipient area, including the accessory optic nuclei. The accessory optic nuclei receives input from On DSGCs, cells that respond to global visual movement, and are responsible for image stabilization. The axons that arise from DSGCs that detect posterior motion seem to belong to a completely different pathway than that of On DSGCs, and thus result in a completely different functional output. At this time, we know only that neurons in particular laminae of the dLGN and SC receive posterior motion input, and those neurons in turn process and project this information to the visual cortex (in the case of the dLGN).


Although the presence of On-Off DSGCs have been known since 1968, the central projections and molecular markers for each subtype of On-Off DSGC have not been fully uncovered. The use of transgenic mice has made this task increasingly easier. This particular subtype of On-Off DSGC was discovered by Huberman et al. in 2009.


Gong S, Zheng C, Doughty ML, Losos K, Didkovsky N, Schambra UB, Nowak NJ, Joyner A, LIblanc G, Hatten ME, Heintz N (2003). A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature 425, 917-925. PubMed Free full text

Huberman AD, Wei W, Elstrott J, Stafford BK, Feller MB, Barres BA (2009). Genetic identification of an On-Off direction selective ganglion cell subtype reveals a layer-specific subcortical map of posterior motion. Neuron 62, 327-334. PubMed Free PMC article

Rivlin-Etzion M, Zhou K, Wei W, Elstrott J, Nguyen PL, Barres BA, Huberman AD, Feller MB (2011). Transgenic mice reveal unexpected diversity of ON-Off direction selective ganglion cell subtypes and brain structures involved in motion processing. J Neurosci. 31, 8760-8769. PubMed Free PMC article