Transmitter concentration at a three-dimensional synapse

At intensities from starlight to 1000-fold brighter, the mammalian rod syna pse transmits a binary signal, the capture of 0 or 1 photon. Zero is signif ied by tonic exocytosis, and 1 is signified by a brief pause. The synapse i s three dimensional: vesicles discharge at the apex of a deep cleft created by the invagination of four postsynaptic processes. Two horizontal cell sp ines bearing alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA ) receptors reach near to the release sites (16 nm), and two bipolar dendri tes bearing mGluR6 receptors end far from the release sites (up to 640 nm). We considered two hypotheses for signal transfer: transmitter quanta might be integrated in the cleft and sensed as a steady concentration thigh for 0 and low for 1); or quanta might be sensed at the postsynaptic membrane as discrete postsynaptic potentials (PSPs) and integrated within the dendrite . We calculate from a passive diffusion model that the invagination empties rapidly (tau similar to 1.7 ms). Further calculations suggest that a gluta mate concentration high enough to hold a bipolar cell in darkness at one en d of its response range would require similar to 4,000 vesicles/s. On the o ther hand, the glutamate pulse from a single vesicle would reach both nearb y AMPA receptors (low affinity) and distant mGluR6 receptors thigh affinity ) at spatiotemporal concentrations matched to their apparent binding affini ties. Thus one vesicle could evoke a discrete PSP in all four postsynaptic processes. We calculate from a stochastic model that PSPs could transfer th e binary signal at similar to 100 vesicles/s. Thus dendritic inte gration o f unitary PSPs is both plausible and 40-fold more efficient than the altern ative mechanism. The rod's deep invagination, rather than serving to pool t ransmitter, may serve to prevent ''spillover'' of transmitter to neighborin g rods. Spillover, by pooling the noise from neighboring rods, would impair transmission of their binary signals.