Maximizing the Presynaptic Voltage Change

underlying visual processing in dim light is well conserved. Individual rod photoreceptors, themselves capable of reliably signaling the absorption of individual photons (6, 9), are pooled in a specialized circuitry referred to as the rod bipolar pathway (17, 49). Following a series of convergent connections in this pathway, the ganglion cells, which are the output cells of the retina, send signals from thousands of pooled rods (57) to higher visual centers. It has been appreciated for more than a half-century that absolute behavioral threshold for light detection requires only a few photon absorptions in this pool (Refs. 4, 26, 53; reviewed in Ref. 23). Several factors influence the transmission of the rod photoresponse through the retina including the fidelity of the rod photoresponse itself, the great degree of convergence of rod signals, and the number of stages of processing. These factors collectively place fundamental limits on the performance of rod vision and thus must each be optimized for single-photon transmission near absolute threshold. Of particular interest is the very first synapse of the rod bipolar pathway, which pools the responses of 20–100 rods and has the unenviable task of discriminating the small graded potential change in the few rods absorbing photons from the remainder of the rods generating electrical noise. The process of rod-to-rod bipolar cell signal transmission has strong implications for setting the absolute threshold for seeing. Indeed, recent experiments on transgenic mice with altered rod photoresponses, due to the lack of the rod photoreceptor protein recoverin, indicate that deficits in absolute visual threshold can be attributable to the properties of rodto-rod bipolar signal transfer (44). Furthermore, mutations in preand postsynaptic proteins that alter the function of this synapse are known to produce visual disorders like congenital stationary night blindness (13, 27, 34, 36, 37). The goal of this review is to highlight the process by which the rod photoresponse traverses the rod-to-rod bipolar synapse to ensure its reliable transmission through the retina. We emphasize the mechanisms that 1) maximize the voltage change sensed by the rod synaptic terminal (called a spherule) following photon absorption, 2) convert this voltage change to a reduction in glutamate release, and 3) remove rod noise postsynaptically. These mechanisms collectively improve the fidelity of the rod single-photon response and allow the retina to transmit these signals to higher visual centers where they contribute to visually guided behavior.