Difference between revisions of "DRD4-RGC"

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[[File:Drd4_huberman_2009.PNG|thumb|right|800px|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]]
 
[[File:Drd4_huberman_2009.PNG|thumb|right|800px|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]]
  
DRD4-DSGCs are On-Off direction selective ganglion cells that express the dopamine receptor D4 (DRD4). They exclusively respond to posterior motion within the visual field (motion towards the nasal pole of the retina). This selective labeling of On-Off DSGCs allowed for characterization of previously unknown brain circuitry and axonal connection pattern of a specific subset of On-Off DSGC.
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DRD4-DSGCs are On-Off direction selective ganglion cells that express the [https://en.wikipedia.org/wiki/Dopamine_receptor_D4 opamine receptor D4 (DRD4)]. They exclusively respond to posterior motion within the visual field (motion towards the nasal pole of the retina). They exhibit the same morphological characteristics as canonical On-Off DSGCs--bistratified, with dendrites touching processes of starburst amacrine cells. Their axons project to specific laminae in the dLGN and the SC. This selective labeling of On-Off DSGCs allowed for characterization of previously unknown brain circuitry and axonal connection pattern of a specific subset of On-Off DSGC.
  
 
==Molecular Marker==
 
==Molecular Marker==
  
These posterior motion-preferring On-Off DSGCs (pDSGCs) are characterized by their expression of Drd4 (dopamine receptor D4). Drd4-GFP BAC transgenic mice express Drd4 prominently in the prefrontal cortex, and also in the ganglion cell layer (GCL) of the retina (Gong et al., 2003, Huberman et al., 2009). Upon further inspection of the retina, dendrites of the GFP positive cells of the Drd4-GFP mouse were found to stratify in two distinct bands in the inner plexiform layer (IPL), suggesting bistratification (Huberman et al., 2009). The GFP positive dendrites appear to be costratified with processes of startburst amacrine cells (SACs).
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These posterior motion-preferring On-Off DSGCs (pDSGCs) are characterized by their expression of Drd4 (dopamine receptor D4). DRD4-GFP BAC transgenic mice express Drd4 prominently in the prefrontal cortex, and also in the ganglion cell layer (GCL) of the retina (Gong et al., 2003, Huberman et al., 2009). Upon further inspection of the retina, dendrites of the GFP positive cells of the Drd4-GFP mouse were found to stratify in two distinct bands in the inner plexiform layer (IPL), suggesting bistratification (Huberman et al., 2009). The GFP positive dendrites appear to be costratified with processes of startburst amacrine cells (SACs).
  
 
[[File:Drd4_transgenic_gong_2003.PNG|thumb|right|400px|Saggital section of Drd4 BAC transgenic mouse brain revealing high expression of Drd4 in the prefrontal cortex. Image adapted from Gong et al., 2003]]
 
[[File:Drd4_transgenic_gong_2003.PNG|thumb|right|400px|Saggital section of Drd4 BAC transgenic mouse brain revealing high expression of Drd4 in the prefrontal cortex. Image adapted from Gong et al., 2003]]

Revision as of 13:22, 22 September 2015

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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

DRD4-DSGCs are On-Off direction selective ganglion cells that express the opamine receptor D4 (DRD4). They exclusively respond to posterior motion within the visual field (motion towards the nasal pole of the retina). They exhibit the same morphological characteristics as canonical On-Off DSGCs--bistratified, with dendrites touching processes of starburst amacrine cells. Their axons project to specific laminae in the dLGN and the SC. This selective labeling of On-Off DSGCs allowed for characterization of previously unknown brain circuitry and axonal connection pattern of a specific subset of On-Off DSGC.

Molecular Marker

These posterior motion-preferring On-Off DSGCs (pDSGCs) are characterized by their expression of Drd4 (dopamine receptor D4). DRD4-GFP BAC transgenic mice express Drd4 prominently in the prefrontal cortex, and also in the ganglion cell layer (GCL) of the retina (Gong et al., 2003, Huberman et al., 2009). Upon further inspection of the retina, dendrites of the GFP positive cells of the Drd4-GFP mouse were found to stratify in two distinct bands in the inner plexiform layer (IPL), suggesting bistratification (Huberman et al., 2009). The GFP positive dendrites appear to be costratified with processes of startburst 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

Physiology

All DRD4-DSGC 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. Responses to drifting graftings reveal strong posterior direction tuning that is more narrowly tuned compared to another type of posterior motion preferring DSGC (TRHR-DSGC).

Left: Responses to drift gratings of DRD4-DSGCs 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.

Anatomy

Dendritic Morphology

DRD4-DSGC 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. 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-DSGC). The cells form a regular mosaic with a relatively high coverage factor (2.99 on average) (Rivlin-Etzion et al., 2011).

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

Retinal Input

Central Projections

DRD4-DSGCs 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-DSGC 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). Inputs to both dLGN and SC arise from the controlateral eye.

DRD4-DSGC 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-DSGC 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).

History

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.

References

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