Ribbon synapses form the first two synaptic elements in the processing of the visual information received by the retina. Ribbon synapses are specialized to release neurotransmitters via synaptic vesicle exocytosis at very high rates. The physiological properties of ribbon synapses have been analyzed in great detail. However, the molecular components that allow ribbon synapse to fulfill their specialized function have not been as fully characterized and studied. In the mouse retina we have recently shown that the synaptic vesicle protein SV2B is found only in ribbon synapses, indicating a specialized role of this protein for ribbon synapses. SV2B is a member of a group of homologous synaptic vesicle proteins (SV2A, SV2B and SV2C) that have been shown to be important regulators of synaptic vesicle exocytosis. Using electro-retino-grams from SV2B knockout mice we could show that the removal of SV2B causes a significant change in the synaptic transmission of the retina. This demonstrates that SV2B is an essential component for the proper functioning of the retina. In further studies we analyzed the molecular and cellular basis of the retina phenotype observed in the SV2B knockout mice. We used a newly developed preparation of mouse bipolar neurons to show that SV2B is involved in the regulation of synaptic Ca2+ levels and synaptic vesicle exocytosis in ribbon synapses from bipolar cells. Further analysis of the retina of SV2B knockout mice revealed a role for SV2B in the regulation of synaptotagmin 1, the Ca2+ sensor for synaptic vesicle exocytosis in ribbon synapses. We will analyze the role of SV2B in rod bipolar synapses by using a combination of electrophysiological recordings, Ca2+ imaging and molecular techniques. In another part of the project we will investigate the role of SV2B in the regulation of synaptotagmin 1 in ribbon synapses. These studies will contribute to a better understanding of the molecular mechanisms regulating synaptic vesicle exocytosis in ribbon synapses of the retina.
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