Purchase this article with an account.
Stuart C. Mangel, Antoine J. Chaffiol, Hee Choi, Masaaki Ishii, Yu Cao, Adewunmi Adelaja, Christophe Ribelayga; Dopamine D1/D2 Receptor System Switches Horizontal Cell GABA-mediated Signaling Back and Forth Between Cones at Night and Cone-Bipolar Cells in the Day. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4331.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
GABAA receptor (GABAAR) expression and activity are increased when intracellular cAMP/PKA increases (Jacob et al., 2008). Because cone-bipolar cell (cBC) dendrites express dopamine D1, but not D2Rs, and cone synaptic terminals express D2, but not D1Rs, cAMP/PKA activity is high in cBC dendrites in the day following prolonged (>30 min) bright light adaptation when their D1Rs are activated, but high in cone terminals at night following prolonged darkness when their D2Rs are not activated by the retinal circadian clock. We therefore examined GABAAR expression and activity of cones and cBCs in the day following prolonged light and dark adaptation and at night following prolonged darkness.
Rabbits and goldfish were light (photopic)-adapted for 1 h in the day or dark (low scotopic)-adapted for 1 h in the day or night. Retinal sections were processed in an identical manner for immunostaining with anti-GABAAR (β2/3) antibodies (rabbits: bd-17; fish: 62-3G1). Double labeling with cell type-specific antibodies determined whether GABAARs are located on cone terminals (zpr-1) and ON-cBC dendrites (Goalpha). The effects of gabazine (GABAAR antagonist) on rabbit cBCs and goldfish cones were studied in the day and night using whole-cell patch-clamp recording.
GABAAR antibody labeling 1) was observed on ON-cBC dendrites, but not cone terminals, following prolonged light adaptation in the day under control conditions but not in the presence of a D1R antagonist, 2) was observed on cone terminals, but not on cBC dendrites, following prolonged darkness at night, and 3) was minimal following prolonged darkness in the day. In the day, following application of dopamine and APB (mGluR6 agonist that blocks cone to ON-BC signaling), rabbit ON-cBCs produced opposite polarity (i.e., hyperpolarizing) surround responses that were blocked by gabazine. Gabazine increased the input resistance of goldfish cones at night, but had minimal effect during the day.
These results suggest that 1) prolonged light adaptation increases D1R activation, which elevates cAMP/PKA, so that GABAAR expression and activity of ON-cBC dendrites are enhanced, producing ON-cBC surrounds via direct GABA-mediated horizontal cell (HC) input to ON-cBC dendrites, and 2) when the retinal clock elevates cAMP/PKA activity in cones at night by decreasing activation of their D2Rs, GABAARs are expressed and active on cone terminals to a greater extent than during the day when the clock activates the D2Rs. When bright illumination in the day activates D1Rs on cBCs, HCs use GABA to signal cBCs, but at night when it is dark and the retinal clock does not activate D2Rs, HCs use GABA to signal cones.
This PDF is available to Subscribers Only