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Christophe Ribelayga, Nange Jin, Lian-Ming Tian, Zhijing Zhang, Eduardo Silveyra, Iris Fahrenfort, Friso Potsma, Paul David, Stephen C Massey; Dissecting Rod and Cone Inputs to OFF Transient Alpha Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2585.
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© ARVO (1962-2015); The Authors (2016-present)
Rod signals can reach retinal ganglion cells (RGCs) through different pathways. It has been proposed that the primary rod bipolar cell [RBC] pathway is the most sensitive and that the secondary (rod-to-cone) pathway operates under intermediate (mesopic) lighting conditions. However, this has never been demonstrated. In addition, the contribution of the tertiary (rod-to-OFF BC) pathway to RGCs remains unknown. Here, we sought to determine the contribution of the different rod and cone inputs to one specific RGC type: the OFF transient alpha RGC (tOFFa RGC), chosen because the primary pathway can be blocked with APB.
We used mice that lack connexinCx36 (Cx36) specifically in cones or in rods and therefore a secondary rod pathway. Isolated retinas were maintained by perfusion and the light responses of single alpha RGCs were recorded using a loose-patch technique. tOFFa RGCs were identified based on (i) light responses and (ii) morphology and stratification following neurobiotin injection and histochemistry.
In WT littermates, tOFFa RGC threshold was ~ 0.001 R*/rod/s (1 photoisomerization per 1,000 rods/s). Application of APB, an mGluR6 agonist that selectively blocks the primary rod pathway shifted the response-intensity curve by ~ 2 log units to the right, consistent with the primary rod pathway being the most sensitive pathway. In the cone-specific Cx36 knock out, tOFFa RGCs had the same sensitivity, suggesting the primary rod pathway was unchanged. However, APB caused a rightward shift of ~ 3 log units due to the block of the primary pathway by APB combined with the absence of the secondary rod pathway. We do not have a selective tool to block the tertiary rod pathway. However, we can estimate the cone threshold by recording from ON alpha RGCs in the pan-Cx36 knock out mice, which have no primary pathway due to the absence of AII/bipolar gap junctions and no secondary pathway due to the absence of rod/cone gap junctions. ON bipolar cells do not make direct contacts with rods so there is no tertiary ON pathway. This approach yielded the cone threshold at ~ 30 R*/rod/s.
tOFFa RGCs receive convergent inputs from all rod and cone pathways. The inputs have different thresholds with the threshold of the primary rod pathway (~ 0.001 R*/rod/s) < secondary (~ 0.1 R*/rod/s) < tertiary (~ 1 R*/rod/s) < cone pathway (~ 30 R*/rod/s).
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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