Biophysical mechanisms of single photon detection

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DESCRIPTION (provided by applicant): The ability of the dark-adapted visual system to detect absorption of a few photons has been known for many years. However, the biophysical mechanisms that make photon detection possible are not understood. Much of rod vision occurs at light levels where photon absorptions occur rarely; thus, failure to transduce single photons or transmit the resulting signals through the retina severely impairs rod vision. Studies of absolute visual sensitivity have made rod phototransduction the best understood of the many G-protein cascades in biological systems and led to a mechanistic understanding of several forms of stationary night blindness. The long-term goal of the proposed work is to bring a similar clarity to understanding of the retinal processing of rod signals and how this processing can fail. Studies of phototransduction will investigate the mechanisms that permit rod photoreceptors to produce a near-identical response to each absorbed photon. The proposed experiments will test the hypothesis that reproducibility is mediated by the shutoff of a single rhodopsin molecule through a series of steps or transitions. This is a substantial departure from conventional models for the shutoff of single molecules. Rhodopsin is one of many G-protein-coupled receptors; thus a similar strategy may decrease variability in signals controlled by other G-protein cascades. The fidelity of signals produced by the rod photoreceptors would be wasted if these responses were not reliably transmitted across the retina. The rod-to-rod bipolar synapse plays a particularly important role as it is the last opportunity to process signals from single rods. The proposed work will determine how much noise is present in the responses of rod bipolar cells, the origins of this noise, and the impact on visual sensitivity. The amplification required for single photon detection presents a risk of saturating retinal signals as light levels increase. Such saturation is prevented by poorly understood adaptational mechanisms working within the retinal circuitry. The proposed work will determine where and how adaptation controls the gain of rod signals at low background light levels. This work will link retinal mechanisms with classic behavioral measures of how visual sensitivity changes with background light.