Synaptic transmission & its modulation in the retina

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DESCRIPTION (provided by applicant): Inhibition is an essential element in retinal information processing. Lateral, inhibitory pathways in the outer and inner plexiform layers modulate the flow of visual information between photoreceptors and bipolar cells, and bipolar cells and ganglion cells, respectively. In mammalian retina, the precise roles of the two lateral pathways are not well understood. GABA (gamma-aminobutyric acid) is an important mediator of inhibition in the retina, and other parts of the CNS. The retina is unique in that two classes of ionotropic GABA receptors, GABAa and GABAc mediate inhibitory signals. These receptors have been shown to have distinct functional properties and cellular distributions in the retina. GABAc receptors, which are found mainly in the retina, mediate longer lasting responses and are more sensitive to GABA than GABAa receptors. GABAa receptors are found on all retinal neurons, whereas GABAc receptors are located mainly on bipolar cell axon terminals and, to a less extent, in the outer plexiform layer (OPL). The goal of the proposed work is to determine how these two classes of GABA receptors participate in the shaping of the visual signal in the mammalian retina. The precise functional roles of GABA receptors in the mammalian retina are unknown. At the inner plexiform layer, GABA is an essential signal for modulating the spatial and temporal aspects of visual information processing. However, it is not known how these inhibitory signals are parsed out by functionally different GABAa and GABAc receptors. Using an animal that lacks GABAc receptors, the GABArho1 null mouse, we will determine the roles of GABAa and GABAc receptors in signal processing in the inner and outer plexiform layers. The proposed research consists of two aims. Aim1 will determine how GABAa and GABAc receptors modulate responses in bipolar cells, which are the first cells that divide the visual signal into distinct channels. Aim 2 will determine how the two classes of GABA receptors give rise to the diversity of spatial and temporal processing at the inner plexiform layer. This aim will also evaluate the relative roles of inner and outer lateral inhibition in shaping ganglion cell responses, the output signals of the retina.