Rod–Driven Retinal Ganglion Cell Responses are Altered by the Absence of GABAC Receptor–Mediated Inhibition

Abstract

Purpose: : GABA plays an important role in mediating inhibition in the retina and shapes its visual output through GABA_A and GABA_C receptors (GABA_CR). This study evaluated the role of GABA_CR–mediated inhibition in shaping the sensitivity and spatial aspects of retinal ganglion cell (RGC) responses under dark adapted conditions.

Methods: : C57B6/J (WT) and GABA_CR null (Null) mice were anesthetized and RGC action potentials were recorded in vivo from the optic nerve, using tungsten electrodes. Receptive field (RF) center size was initially determined under light adapted conditions (20cd/m²) using spot stimuli of varying diameter. The mouse was then dark adapted for 20 minutes and the same cell’s sensitivity was assessed using an optimal spot of increasing brightness on a 0 cd/m² background. Spatial aspects of each RGC’s receptive field also were evaluated using spots (3cd/m²) of varying diameters.

Results: : Under dark adapted conditions, detection thresholds for an optimal spot were higher for Null ON–center RGCs than for WT cells. In response to a supra threshold spot of optimal size, WT ON–center RGCs displayed an increase in spiking (excitation), which surprisingly was significantly larger than that of Null RGCs. In WT cells, a decrease in firing rate (post stimulus inhibition) occurred when the center stimulus was removed. However, in Null RGCs, the post stimulus inhibition was greatly reduced in magnitude, regardless of spot diameter, compared to WT cells. At light adapted levels, no loss of this post stimulus inhibition was evident in Null vs. WT ON–center RGCs.

Conclusions: : GABA_CR–mediated inhibition plays an important role in rod driven receptive field center responses in ON–center RGCs. The loss of GABA_CR–mediated inhibition elevates the dark adapted threshold and reduces the amplitude of the receptive field center response. A loss of inhibition that occurs when center stimulation is removed appears to be completely attributable to GABA_CR–mediated inhibition, but only when RGCs receive input via the rod pathway. Our results suggest that GABA_CR–mediated inhibition differentially influences rod and cone pathway signals to RGCs. This is consistent with previous findings that show larger GABA_CR mediated currents in rod vs. cone bipolar cells.

Keywords: retina: proximal (bipolar, amacrine, and ganglion cells) • electrophysiology: non-clinical • inhibitory receptors