Mammalian retinas are capable of responding to over a 50 billion-fold change in ambient light throughout the day. Research has shown that the release of nitric oxide, activity of potassium channels, and activity of glutamate receptors in the retina are all affected by changes in the mean ambient light level. In this thesis I investigate how these modify visual signal processing in the light-adapted retina by performing whole-cell patch-clamp recordings of mouse retinal ganglion cells The nitric oxide-cGMP signaling pathway is one of the most widespread throughout the retina, so it has been linked to a diverse array of physiological functions in the retina. Researchers have determined nitric oxide is responsible for modulating light responses, triggering glutamate release, stimulating GABA release, inhibiting glycine release, and modulating cyclic nucleotide-gated channels in the retina. My research has revealed that inhibiting nitric oxide synthase in the light-adapted retina reduces the sensitivity of retinal ganglion cells to light stimuli by diminishing excitatory neurotransmission Large-conductance calcium-activated potassium (BKCa) channels have been located in several different cell types in the retina, including rods, bipolar cells, amacrine cells, and ganglion cells. However, immunological evidence does not suggest BKCa channels are expressed in mammalian cones. In this study I find dramatic physiological differences between BK Ca channel activity in the rod-driven and cone-driven retina by using BKCa channel blockers Ionotropic and metabotropic glutamate receptors have varying levels of expression along the On and Off cone pathways in the retina. For instance, On-cone bipolar responses have been shown to be driven by mGluR6 receptors and Off-cone bipolar cells driven by AMPA and kainate receptors. The findings from my research suggest that mGluR6 affects Off signaling via crossover inhibition. Additionally, blocking ionotropic glutamate receptors eliminates Off responses by acting on Off-cone bipolar cells and reduces On responses by acting on ganglion cells in the light-adapted retina. The results contained in this thesis have provided for a detailed analysis of how numerous physiological processes contribute to the ability of the mammalian retina to adapt to the enormous range of ambient light levels encountered throughout the day
