The retina detects and transmits large amounts of visual information quickly and reliably. Ribbon synapses are key components of the vertebrate retinal circuitry, forming the first and second presynaptic elements in the signaling pathway to the brain. The specialized morphology and function of the ribbons presumably endows them with a unique capacity for copious and fast neurotransmitter release, which is thought to be essential for the efficient processing and encoding of visual information. Nevertheless, the underlying cellular mechanisms that modulate and maintain transmitter output from ribbon synapses under vastly different ambient light conditions are poorly understood. Due to their large size, we are able to patch-clamp single goldfish bipolar cell terminals. This allows us to measure both presynaptic Ca currents and evoked changes in membrane capacitance that assay synaptic vesicle exocytosis and endocytosis in real time from a living nerve terminal. We have found that the reciprocal synapse of bipolar cells undergoes short-term synaptic depression. We will determine the underlying mechanisms responsible for this depression. The first hypothesis to be tested is that synaptic vesicle pool depletion at GABAergic amacrine cells, and desensitization of GABAA and AMPA receptors, contribute to depression and largely determine the recovery rate. We also find that bipolar cell terminals have a tonic inhibitory current mediated by high affinity GABAC receptors that do not desensitize. Thus the second hypothesis is that different subtypes GABA transporters in amacrine cells set the level of this tonic inhibitory current. We also have preliminary evidence that the acidity of synaptic vesicles and the process of filling synaptic vesicles with glutamate may involve chloride channels on the vesicle membrane. Biochemical studies of this process are controversial and few studies have been done in intact nerve terminals. We will thus study this process in the bipolar cell terminal embedded in a retinal slice. These studies should increase our basic understanding of signal processing in the retina and they may be relevant to retinal diseases that degenerate photoreceptors, but spare ganglion cells. A prosthetic device that stimulates the remaining neurons might restore some sight to blind people. However, this stimulation has to encode visual information at the same high rates that bipolar cells do in normal retinas. A better understanding of how bipolar cells release glutamate to excite ganglion cells will thus lead to insights on how to develop a retinal prosthesis using more physiologically relevant patterns of stimulation that match more closely the original information rates of bipolar cells. Our studies will thus hopefully aid in the future design of more efficient retinal prosthesis devices.
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