TRHR-RGC

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On-Off DSGC from TRHR-GFP mouse filled with Alexa fluor 594. Yellow arrows show "looping" arborizations characteristic of mouse DSGCs. Scale = 50um. Image adapted from Rivlin-Etzion et al., 2009

TRHR-RGCs are retinal ganglion cells that express thyrotropin-releasing hormone receptor (TRHR). 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). TRHR-RGCs have bistratified dendrites and receive synaptic input from starburst amacrine cells, like other On-Off DSGC types. Their axons project to the dorsal and ventral lateral geniculate nucleus, the superior colliculus, and the zona incerta. Although they prefer the same direction of motion DRD4-RGCs, they are more broadly tuned, slightly more symmetrical in dendritic arbor, and project to a broader range of areas.

Molecular definition

These retinal ganglion cells are defined by their expression of TRHR (thyrotropin-releasing hormone receptor). They can be visualized in TRHR-GFP BAC transgenic mice, in which GFP is expressed under the control of the Trhr promoter (GENSAT). This mouse line labels two populations of cells in the retina, one in the ganglion cell layer (GCL) and one in the inner nuclear layer (INL). The GFP-positive cells in the GCL are a type of DSGC, while the GFP-positive cells in the INL are amacrine cells.

GFP positive cells in TRHR-GFP retina with no immunostaining. A. Whole mount retina. Scale = 500um. B. Green framed region showing GFP positive RGCs. scale = 100um. C. Blue framed region showing GFP positive amacrine cells and RGCs (yellow arrows). Scale = 100um. D. TRHR-GFP retina stained for GFP. E. TRHR-GFP retina stained for VAChT. F. Merge of GFP (green) and VAChT (green). Yellow arrow points to RGC. Scale = 25um. Image adapted from Rivlin-Etzion et al., 2011

Physiology

TRHR-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. The average ON response is longer compared to another type of posterior motion preferring DSDG (DRD4-RGC). Responses to drifting graftings reveal strong posterior direction tuning that is more broadly tuned than the DRD4-RGC.

Left: Responses to drift gratings of TRHR-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=80). Adapted from Rivlin-Etzion et al., 2011.

Anatomy

Dendritic Morphology

TRHR-RGC cells exhibit canonical morphological characteristics of On-Off DSGCs. They are bistratified, costratifying with starburst amacrine cell (SAC) processes. Their dendritic arbors exhibit "looping" patterns prevalent in mouse On-Off DSGCs. Their dendritic arbors are symmetric, with somas resting in the center of their dendritic fields, in contrast to DRD4-RGCs, which are slightly asymmetric. The cells form a regularly spaced mosaic with an average soma spacing of 63um (Rivlin-Etzion et al., 2011).

Mosaic of four TRHR-RGCs. Bistratification of dendrites can be seen below. Scale= 100um. Image adapted from Rivlin-Etzion et al., 2011

Retinal Input

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

Central Projections

TRHR-RGCs send their axons to several areas of the brain: the dorsal and ventral lateral geniculate nucleus (dLGN and vLGN), the superior colliculus (SC), and the zona incerta (ZI). In the dLGN, TRHR-RGCs send their axons to a thin layer medial to the optic tract, in the same area that which DRD4-RGCs project to. They also innervate the lateral portion of the vLGN, which receives little projection from DRD4-RGCs. In the SC, they project to the lower stratum griseum superficialis (lSGS), much like DRD4-RGCs, although their terminations are more patchy (Rivlin-Etzion et al., 2011, Huberman et al., 2009). The ZI, a forebrain area ventral to the vLGN, also receives input from TRHR-RGCs.

TRHR-RGC axons terminate in a laminar distribution throughout the dLGN and vLGN. A. The LGN labeled with CTb-594. B. The LGN labeled with GFP, showing where TRHR-RGC axons project to. Arrows indicate projetions to the ZI. C. Merge of both CTb and GFP. scale = 250um. Image adapted from Rivlin-Etzion et al., 2011.
TRHR-RGC axons terminate in a clear laminar distribution throughout the upper stratum griseum superficialis (uSGS). B. RGC axons labeled with CTb-594. D. Axons of TRHR-RGCs terminate in the lSGS in clumps. F. Axons of DRD4-RGCs also terminate in the uSGS, although in a more uniform fashion. Scale = 250um. Image adapted from Rivlin-Etzion et al., 2011
Interestingly, TRHR-RGC axons also project to the zona incerta (ZI). Scale = 30um. D'. RGC axons stained with CTb-594. E'. TRHR-RGC axon terminations within the ZI stained with GFP. F' Merge of both. Image adapted from Rivlin-Etzion et al., 2011

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 Rivlin-Etzion et al. in 2011.

References

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