OFF-Center Retinal Ganglion Cell Responses Are Altered by the Absence of GABAC Receptor-Mediated Inhibition

Abstract

Purpose: : GABA shapes retinal visual output through GABA_A and GABA_C receptors (GABA_CR). While GABA_CRs are expressed in the OFF sublamina of the inner plexiform layer and mediate GABA evoked currents in Off cone bipolar cells, no clear functional role for GABA_CR-mediated inhibition has been reported for light evoked responses in the Off pathway. This study evaluated the role of GABA_CR-mediated inhibition in shaping spontaneous activity (SA) and OFF-center retinal ganglion cell (RGC) receptive field (RF) organization.

Methods: : C57Bl/6J (WT) and GABA_CR null (Null) mice were anesthetized and RGC action potentials recorded in vivo from the optic nerve under light-adapted conditions (20 cd/m²), using tungsten electrodes. SA was assessed and receptive filed (RF) organization characterized with spots of varying diameter. Two types of spots were used, each 67% contrast: bright or opposite contrast spots (OCS) and dark or same contrast spots (SCS) (100 and 3 cd/m²). Peak firing rate of each RGC was plotted as a function of spot size, to generate an area response function (ARF). The spatial tuning of each RGC’s RF was quantified by measuring the slopes of the ascending (center summation strength) and descending (surround antagonism) ARF limbs.

Results: : The SA of Null OFF-center RGCs was significantly higher than WT. When SCS were presented, Null OFF-center RGCs responded in a manner similar to WT. However, in response to OCS, the spatial tuning (both center summation and surround antagonism) of Null OFF-center RGCs was significantly reduced compared to WT.

Conclusions: : These findings represent the first demonstration of a functional role for GABA_CR-mediated inhibition in the response properties of OFF-center RGCs. GABA_CR-mediated inhibition regulates the SA of OFF-center RGCs and improves their RF spatial tuning when opposite contrast stimuli drive the response. Although reduced, surround inhibition is not eliminated in Null OFF-center RGCs, suggesting that other inhibitory mechanisms also contribute to RF spatial tuning. These findings support the notions that the RF surround is composed of multiple mechanisms and that different inhibitory receptors function under different stimulus conditions.

Keywords: ganglion cells • inhibitory receptors • electrophysiology: non-clinical