Effects of GABA(C)R and mGluR1 antagonists on contrast response functions of Sprague-Dawley and P23H rat retinal ganglion cells

The GABA(C)R antagonist TPMPA and the mGluR1 antagonist JNJ16259685 have been shown previously to alter the sensitivity of retinal ganglion cells (RGCs) in the Sprague-Dawley (SD) rat and P23H rat (animal model of retinitis pigmentosa) to brief flashes of light. In order to better understand the effects of these antagonists on the visual responses of SD and P23H rat RGCs, I examined the responses of RGCs to a drifting sinusoidal grating of various contrasts. Multielectrode array recordings were made from RGCs to a drifting sinusoidal grating of a spatial frequency of 1 cycle/mm and a temporal frequency of 2 cycles/s. In both SD and P23H rat retinas, contrast response functions were found to have a variable shape across cells. Some cells showed saturation of responses at high contrast levels while others did not. Whereas 49% of SD rat RGCs exhibited response saturation, only 14% of P23H rat RGCs showed response saturation. TPMPA decreased the responses of saturating SD rat RGCs to low (6% to 13%) grating contrasts but increased the response to the highest contrast (83%) tested. JNJ16259685 did not significantly affect the contrast response functions of either saturating or non-saturating SD rat RGCs. In contrast, both TPMPA and JNJ16259685 increased the responses of saturating and non-saturating P23H rat RGCs to all grating contrasts. Neither TPMPA nor JNJ16259685 affected the contrast thresholds of SD rat RGCs, but both antagonists lowered the contrast thresholds of P23H rat RGCs. Overall, the findings show that GABA(C)R and mGluR1 antagonists have differential effects on the contrast response functions of SD and P23H rat RGCs. Notably, these receptor antagonists increase the responsiveness of P23H rat RGCs to both low and high contrast visual stimuli.