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Rebekah Anne Warwick, Michal Rivlin-Etzion; Dopamine differentially affects rod and cone circuits that underlie the response of transient-OFF-alpha retinal ganglion cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1590.
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© ARVO (1962-2015); The Authors (2016-present)
Dopamine depletion in the retina occurs in Parkinson’s disease and is thought to be a pre-motor marker that could be utilized for early diagnosis. Yet, the role of retinal dopamine is not fully understood. Previous research indicated that dopamine enhances the antagonistic surround of retinal ganglion cell (RGC) receptive fields. We examined the effects of dopamine depletion on one subtype of RGC, the transient-OFF-alpha RGC (tOFFα-RGC).
We carried out two-photon targeted electrophysiological recordings of tOFFα-RGCs under control conditions and in the presence of the D1 receptor antagonist - SCH23390 (1 μM). We used visual stimuli of black spots on a grey background centered on the cell soma. Spot diameters varied from 50-800 μm to assess the cell’s receptive field.
Under control conditions tOFFα-RGCs exhibited OFF responses which had a maximal firing rate with the 300 μm spot, corresponding to the size of their dendritic tree (n=15 cells). Increasing the spot size decreased the responses as a result of activating the antagonistic surround. Voltage clamp revealed that both excitation and disinhibition contributed to the OFF response (n=5 cells). Under D1 receptor blockade, tOFFα-RGCs did not display a reduction in their maximal firing rates between the 300 and 800 μm spots, suggesting a weakened surround (n=22 cells). Yet, surprisingly 14/22 cells displayed ON responses with larger spot sizes (600-800 μm), an event that would suggest an increase in surround strength. Voltage clamp revealed that while excitation exhibited a decrease in surround strength, disinhibition exhibited an increase in surround strength, to the extent that a gain in inhibition was observed with larger spot sizes (600-800 μm; n=5 cells).
The known major inputs to tOFFα-RGCs are glutamatergic (excitatory) input from OFF cone bipolars and glycinergic (inhibitory) input from AII amacrine cells that are part of the primary rod pathway. Our results suggest that dopamine differentially affects the different pathways underlying the response of tOFFα-RGCs, increasing the surround via the cone circuits and decreasing it via the primary rod circuit.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
TOFFα-RGC receptive fields are altered under dopamine blockade. Top: Different sized spot stimuli. Mean firing rate of tOFFα-RGCs in control (middle) and following D1 blockade (bottom). Yellow ellipse indicates ON response.
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