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PB Cook; Modulation of Synaptic Inputs to Ganglion Cells by Nitric Oxide . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1948.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Nitric oxide is produced by many retinal neurons, however its ability to modulate synaptic activity in the inner retina is poorly understood. I examined how nitric oxide modulates the excitatory and inhibitory synaptic inputs to ganglion cells evoked by light and by focal electrical stimulation. Methods: I recorded postsynaptic currents from ganglion cells using whole-cell patch clamp techniques in retinal slices prepared under infrared illumination. Responses were elicited by a green LED (1 sec duration) and by brief focal electrical stimulation (zap; 1 msec; .1 - 1.5 µA) of the outer-plexiform layer. Strychnine (10 µM) was used to isolate the GABAergic inputs. Results: Nitric oxide has been shown to affect photoreceptor calcium currents, so I compared responses elicited by illumination with those elicited by the zap, which directly depolarizes bipolar cells to activate inputs to the inner plexiform layer. Application of the nitric oxide donor, NONOate (100 µM) rapidly (< 1 min) reduced or eliminated light- and zap-evoked IPSCs in ganglion cells. In contrast, NONOate reduced or eliminated the light-evoked EPSCs, but not the zap-evoked EPSCs, indicating that the reduction of light-evoked responses in the inner retina is mostly a result of modulation in the outer retina. NONOate frequently increased the duration of the zap-evoked EPSC, probably as a result of reducing feedback from amacrine cells to bipolar cells. The effect of a brief application of NONOate (1 min) was rapidly reversible and reduced currents at the onset and offset of light equally, indicating that NONOate is altering the output of photoreceptors. Conclusions: Nitric oxide appears to have distinct actions in the outer in inner retina. Light-evoked signals from the outer retina are reduced or blocked by nitric oxide, possibly by altering photoreceptor output. In the inner retina, nitric oxide reduces IPSCs, not by decreasing bipolar cell output, but probably by modulating amacrine cell output.
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