GABAc Receptors Mediate Ganglion Cell Lateral Inhibition During Weak, but Not Strong Surround Illumination

Abstract

Abstract: : Purpose: Ganglion cell light sensitivity is determined, in part, by lateral inhibitory signaling in the outer and inner retina. We used pharmacological and electrophysiological methods to determine the roles of inner retinal GABA receptors on ganglion cell light sensitivity. Methods: Light responses of ganglion cells were recorded with whole-cell patch clamp techniques in the salamander retinal slice. Slices were stimulated with either full-field illumination, or a 200µm spot, with or without, surround illumination. Intensity-response relationships were constructed by plotting responses versus the Log₁₀ of the stimulus luminance. For all experiments, glycine receptors were blocked with strychnine. Receptor-specific blockers were used to determine the subtypes of GABA receptors that contribute to changes in ganglion cell sensitivity. Results: For full-field stimuli, light-evoked (L-)EPSCs increased as a function of illumination intensity and were well fit by a sigmoid curve. The ganglion cell sensitivity curve was not affected by the GABA_A antagonist bicuculline. However, GABA_C antagonists picrotoxin and I4AA, applied in addition to bicuculline, shifted the curve to the left and steepened it. In contrast, when GABA_C receptor activation was increased by NO-711, a GABA transporter-1 inhibitor, the curve shifted to the right and broadened. This suggests that GABA_C receptors are able to regulate ganglion cell light sensitivity. GABA receptor blockers did not affect L-EPSCs evoked by spot illumination, indicating that the GABA_C receptors were activated by lateral inhibition in the inner plexiform layer (IPL). The spot intensity-response curve was shifted to the right and compressed by the surround illumination. GABA_C, but not GABA_A, receptor antagonists blocked the effects of dim surrounds. Strong surround illumination produced a larger reduction of the ganglion cell spot responses, however, inhibition was not affected by GABA receptor blockers. Conclusion: For weak surround activation, GABA_C receptors mediate lateral inhibition at the inner retina, controlling ganglion cell sensitivity to spot illumination. Strong activation of the surround produced a further decrease in ganglion cell sensitivity, which was not mediated by GABA_A or GABA_C receptors.

Keywords: 439 inhibitory neurotransmitters • 557 retina: proximal(bipolar, amacrine, and ganglion cells) • 559 retinal connections, networks, circuitry