VISUAL SIGNALLING IN RETINA

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We propose to study visual signalling in the mammalian retina. One group of experiments will focus on visual transduction, while a second will focus on the neural circuits over which transduced signals flow to the retinal ganglion cells. The experiments on visual transduction will examine the still poorly- understood processes that terminate the response to light. By making electrical recordings from transgenic mouse rods as well as normal primate photoreceptors we will ask: 1. Must rhodopsin be phosphorylated in the C terminal region for its catalytic activity to shut off normally in vivo? When does phosphorylation occur? Is phosphorylation at a single site sufficient to elicit complete shutoff? 2. Must arrestin bind to phosphorylated rhodopsin to complete shut-off? When does arrestin bind? How much does phosphorylation alone reduce catalytic activity? 3. Does the Ca-binding protein recoverin, which regulates rhodopsin shutoff, make the single photon response reproducible, mediate the gain reduction that occurs in background light, or both? 4. What molecular defect in rhodopsin is responsible for the anomalously- prolonged single photon responses that occur in normal primate rods? Is older rhodopsin more likely to be defective? 5. What are the dynamics of intracellular Ca in primate cones, and how do they relate to the diphasic waveform of the cone flash response? The experiments on neural circuitry will use a multielectrode array to record from ganglion cells in isolated primate retinas. We will ask: 6. How do the receptive fields of populations of ganglion cells sample visual images? 7. Do ganglion cells in the primate retina undergo concerted firing or do they only signal independently? If concerted firing is present, what cells are involved, over what length scale are signals correlated, and how does concerted firing contribute to the detection of contrast and color? 8. What is the contribution to ganglion cell receptive fields of electrical coupling between photoreceptors and horizontal cell feedback on photoreceptors? 9. Are the cones themselves the dominant site of chromatic adaptation in the retina, or are downstream cells involved? Can adaptation of one cone class change the gain of signals from another cone class?