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MM Wang, LJ Frishman, DM Sherry; Distribution and Expression of Vesicular Glutamate Transporters in Developing Mouse Retina . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2706.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Vesicular glutamate transporters (VGLUTs) transport glutamate, the major excitatory neurotransmitter in mammalian retina, into synaptic vesicles. Two VGLUTs (VGLUT1 and VGLUT2) have been identified recently and display complementary distributions in the glutamatergic synapses of the brain. This suggests a difference in vesicular glutamate uptake, presumably related to synaptic function. Understanding the developmental expression of VGLUTs will improve our understanding of glutamatergic synapses in the retina and how glutamatergic circuits form and mature. Methods: The expression of VGLUT1 and VGLUT2 was examined in developing and adult retinas from C57BL/6 wildtype mice, using single and double immunolabeling. Results: In adult retina, VGLUT1 immunoreactivity (-IR) was restricted to ribbon synapses of photoreceptors and bipolar cells in the OPL and IPL, respectively, as confirmed by double labeling with the ribbon synapse-specific marker SV2B (Wang et al., 2001). VGLUT1-IR was present in developing photoreceptor and bipolar terminals by the time their ribbon synapses can first be identified ultrastructurally at postnatal day 5 (P5) and P10, respectively. VGLUT1-IR was first detected in presumptive photoreceptors at P2 and in bipolar terminals at P8. Double labeling with SV2B showed that VGLUT1-IR was restricted to OFF bipolar terminals at P8, and did not become detectable in ON bipolar terminals until P10. In contrast, other presynaptic proteins involved in neurotransmitter exocytosis (e.g., SV2B) appeared concurrently in developing ON and OFF bipolar terminals. Double labeling for VGLUT1 with cell-specific markers indecated that VGLUT1 was not expressed in glycinergic, cholinergic or dopaminergic terminals throughout development. VGLUT2-IR was not detected in any synaptic terminals during development and adulthood, although some labeling was present in cell bodies in the nuclear layers. Conclusion: VGLUT1, rather than VGLUT2, is expressed at retinal ribbon synapses. VGLUT1 and other synaptic proteins associated with vesicular transmitter release are present in photoreceptor and bipolar terminals by the time ribbon synapse formation is initiated, suggesting that ribbon terminals may be capable of vesicular glutamate release shortly after initial contact with the target is made. If OFF bipolar terminals mature prior to ON bipolar terminals with respect to the ability to load glutamate into vesicles, then OFF bipolar circuits could become functional slightly before ON bipolar cells.
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