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R. Farajian, S. A. Bloomfield; Gap Junction-Mediated ON Signals in OFF Alpha Ganglion Cells are Unmasked by Blockade of GABAergic Inhibition. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1519.
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© ARVO (1962-2015); The Authors (2016-present)
To study the masked synaptic signals received by OFF alpha ganglion cells in the rabbit retina.
OFF alpha ganglion cells were visualized with the vital dye Azure B under infrared transcleral illumination of a flattened, living retinal preparation of the albino rabbit. Light-evoked responses were recorded with extracellular and intracellular microelectrodes before, during, and after the administration of various pharmacological agents. OFF alpha cells were subsequently labeled with Neurobiotin for morphological identification.
Application of 100 µM picrotoxin (PTX) unmasked a brisk, short-latency ON response in recordings from OFF alpha ganglion cells. In addition, we occasionally observed a distinct, longer-latency ON response similar to that described recently (Rentería et al., 2006). Interestingly, neither the selective GABAA receptor blocker SR95531 (20 µM) nor the GABAC blocker TPMPA (100 µM) alone could unmask the short-latency ON response. Only in combination could the two blockers unmask the ON response, indicating that it is normally inhibited by pathways utilizing both GABAA and GABAC receptors. Application of AP4 (100 µM), in the presence of GABA blockade, reversibly eliminated the short-latency, but not the long-latency, ON response in OFF alpha cells, indicating that the former is derived from the ON pathway. How OFF alpha cells, whose dendrites stratify exclusively within sublamina-a of the IPL, receive the masked ON signal remains unclear. However, application of the gap junction blockers MFA (100 µM) or 18β-glycyrrhetinic acid (25 µM) reversibly eliminated the short-latency ON response, suggesting that it is received via the gap junctions OFF alpha cells make with neighboring wide-field amacrine cells.
Our results indicate that OFF alpha cells receive ON signals that are normally suppressed by GABAergic inhibition. Both GABAA and GABAC receptors underlie this suppression, implicating feedforward and feedback inhibitory pathways in the IPL. Our data suggest that the ON signals are relayed to OFF alpha cells via the gap junctions made with neighboring amacrine cells. Overall, our results indicate an unexpected complexity in the communication and interaction of ON and OFF signals in the proximal retina.
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