Abstract
Purpose: :
Ganglion cells (GCs) display a center-surround receptive field (RF) following prolonged (>30 min) light adaptation, but exhibit minimal surrounds following prolonged dark adaptation (Barlow et al., 1957). Bipolar cell (BC) surround strength also decreases when the background illumination is reduced (Fahey & Burkhardt, 2003). Under light-adapted conditions, horizontal cells (HCs) contribute to ON-GC surrounds (Mangel, 1991) possibly by releasing GABA (Guo et al., 2010) directly onto ON-cone BC (cBC) dendrites, which express Cl-permeable GABAA receptor (GABAAR) channels and the Cl cotransporter NKCC. We thus tested whether light/dark adaptive regulation of GABAARs and NKCC modulates direct, GABA-mediated HC signaling to ON-cBC surrounds.
Methods: :
Rabbits were bright light (photopic)- or dark (low scotopic)-adapted for 1 h or rabbit retinas were incubated in Ringer for 1 h under light-adapted conditions with or without test drugs. Retinal sections were processed in an identical manner for immunostaining with antibodies against the β2/3 subunit-containing GABAAR (bd-17) and NKCC (T4). The effects of current injections into HCs on the activity of nearby ON-GCs in rabbit eyecups and application of dopamine, APB (mGluR6 agonist that blocks cone to ON-BC signaling), and gabazine (GABAAR antagonist) on cBCs in rabbit retinal slices were studied.
Results: :
Intense GABAAR and NKCC antibody labeling were observed in ON-BC dendrites under light-adapted control conditions, but both immunosignals were minimal in dark-adapted retinas or in light-adapted retinas pre-treated with the dopamine D1R antagonist SCH23390. Under light-adapted conditions, picrotoxin (GABAA/C antagonist) and bumetanide (NKCC inhibitor) blocked the effect of HC polarizations on ON-GC spike activity. Picrotoxin also eliminated the reduction in the ON-GC center response produced by hyperpolarizing HCs. Dopamine application and prolonged light adaptation decreased the RF center size and strengthened the RF surround of ON-cBCs. Following APB application in the presence of dopamine, ON-cBCs produced opposite polarity (i.e., hyperpolarizing) surround responses that were blocked by gabazine.
Conclusions: :
These results suggest that prolonged light adaptation increases D1R activation so that GABAAR and NKCC expression and activity of ON-cBC dendrites are enhanced, producing the RF surrounds of ON-cBCs and ON-GCs via direct GABA-mediated HC excitation of ON-cBC dendrites. Conversely, the decrease in D1R activation following prolonged darkness substantially reduces GABAAR and NKCC expression and activity, weakening ON-cBC and ON-GC surrounds.
Keywords: receptive fields • inhibitory receptors • ion transporters