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T. Ichinose, P. D. Lukasiewicz; Excitatory Amino Acid Transporters in Rod Bipolar Cells Contribute to Visual Information Processing. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4801.
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© ARVO (1962-2015); The Authors (2016-present)
The excitatory amino acid transporter EAAT5 is found on retinal rod bipolar cell (RBC) terminals. We previously showed that light-evoked glutamate release elicits EAAT-mediated Cl- currents in RBCs. Thus EAAT5 may act as a presynaptic inhibitory glutamate receptor. Here, we show that EAAT5 activation shapes visual signals.
Whole-cell recordings were made from RBCs in dark-adapted mouse retinal slices. RBCs were identified by including sulforhodamine B in the pipette. Light responses were evoked with either full-field illumination or different sized light spots. EAAT-mediated Cl- currents were isolated by blocking glycine and GABA receptors. RBC glutamate release was studied by monitoring FM1-43 unloading from RBC terminals in wholemount retinas using confocal microscopy.
To determine the effects of EAATs on visual processing, we recorded L-EPSPs in RBCs while puffing an EAAT agonist or antagonist onto their terminals. The agonist, D-aspartate, decreased L-EPSPs, while the antagonist, TBOA, enhanced L-EPSPs, indicating that EAATs reduce visual signaling in RBCs. To investigate whether EAATs regulate the output of RBCs, we monitored FM1-43 labeling in RBC terminals. CPPG, a mGluR6 antagonist, depolarized RBCs and unloaded FM1-43, attributable to vesicular release. Activating EAATs with D-aspartate slowed the FM1-43 unloading, whereas blocking EAATs with TBOA accelerated unloading, indicating that EAATs modulate glutamate release from RBCs. We found that EAAT- and GABA receptor-mediated inhibition differed in RBCs: the spatial extent of EAAT-mediated inhibition was narrower than GABA receptor-mediated inhibition, and the spontaneous EAAT currents were more prolonged than GABAergic currents.
EAATs affect visual processing by regulating light responses and glutamate release from RBCs. EAAT-mediated inhibition is functionally distinct from GABAergic inhibition, exhibiting a lower light sensitivity, a narrower spatial extent, and a slower time course than GABA inhibition. The distinct properties of EAAT- and GABA receptor-mediated inhibition in RBC terminals complement each other to shape visual signaling.
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