The long-term objective of this project is to provide a quantitative description of the mechanism of signal transmission at the basal synapse between a mammalian cone photoreceptor and an Off bipolar cell. Basal synapses are structurally different from conventional synapses: At basal synapses, the membranes of a cone and Off bipolar cell come into close apposition, but there are no obvious presynaptic docked vesicles or active zones. Indeed, while cones release the transmitter glutamate and Off bipolar cells have receptors for glutamate, little else is known about how basal synapses work. It is important to know how basal synapses work because cones are the sole mediators of vision in bright light, and basal synapses are the first link in a pathway that signals light decrements (i.e., approximately 50% of vision) to the rest of the brain. Results obtained during the previous grant period suggest that glutamate is released predominantly at ribbon synapses located atop membrane invaginations and must diffuse an unusually long distance, 200 - 500 nm, to reach glutamate receptors at basal contacts.
The aim of the current proposal is to understand how the glutamate spatiotemporal concentration gradient at the basal surface of a cone influences transmission to different types of postsynaptic Off bipolar cells. Two main ideas are investigated: The first idea is that the different morphological types of Off bipolar cells each receive a different signal at the cone synapse, in part because their dendrites contact cones and sample the concentration gradient at characteristic distances from ribbon release sites. The second idea applies specifically to Off bipolar cells that make relatively distant contacts. In that case, diffusion would be expected to smear and attenuate the time course of synaptic quantal events, and could act as a filter to decrease undesirable quantal noise, thereby increasing the sensitivity of the synapse. Information about how far glutamate must diffuse to reach Off bipolar cell receptors will be obtained from voltage clamp recordings of quantal events in Off bipolar cells and the characterization of receptor kinetics. The spatial inter-relations of individually labeled Off bipolar cell dendrites at the cone basal surface will be studied with confocal microscopy. The basal surface of a cone pedicle is a complex synaptic structure which would likely need to be reproduced should cones be transplanted or otherwise regenerated. ? ?
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