At the first synapse in vision, the release of glutamate from photoreceptor terminals exerts distinct actions at On and Off bipolar cells. This divergent design of the retinal circuit forms the basis for two pathways, each coding light intensities of opposite signs, each integral to the flow of visual information to later neurons. The proposal below addresses questions central to understanding how On and Off synapses in the mammalian retina operate: 1) what are the different types of receptors that are present at the different bipolar cell synapses, 2) what functional contributions does each receptor type make to the overall amplitude and timecourse of the excitatory post synaptic current, 3) what is the role of desensitization at the post- synapse, and 4) what is the timecourse of vesicle release, depletion and replenishment at photoreceptor terminals. Answers to these questions lead to an understanding not only of cellular processing at these critical synapses but also allow for identification of the cellular mechanism of the defects in clinical animal models, such as congenital stationary night blindness and muscular dystrophy, where synaptic transmission is compromised but its defect is unknown.
