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A Akopian; Paired-pulse Modulation of On- and Off-EPSCs in Retinal Ganglion Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4761.
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Purpose: Short-term changes in excitatory postsynaptic potentials, resulting from different stimulation paradigms, play an important role in controlling the spiking patterns of retinal ganglion cells. In the present study the modification of On- and Off-excitatory postsynaptic currents (EPSCs) in salamander retinal ganglion cells by paired-pulse light stimulation was studied. Methods:Whole-cell patch clamp recordings of EPSCs from On-Off ganglion cells were made in a slice preparation. LAP4 was used to block On bipolar cell and AP7 to block NMDA receptors. Results:Paired-pulse stimulation resulted in a depression (PPD)of On-EPSCs and a facilitation (PPF) of Off-EPSCs. The PPF, but not the PPD depended strongly on stimulus duration. Both PPD and PPF were reduced exponentially by increasing interstimulus interval (ISI) to 20 s. At 1s duration and 1s ISI, the ratio of the amplitude of the second On-EPSC to the first one, (paired-pulse ratio), was 0.2 ± 0.04 (mean +/-SE), while the paired-pulse ratio for the Off-EPSC was increased dramatically to 2.3 ± 0.04. PPF of Off-EPSC was abolished by the NMDA antagonist AP7. Paired-pulse- induced changes in postsynaptic responses were more evident in voltage clamp compared to current clamp mode. LAP4 blocked On-EPSCs but enhanced Off-EPSCs evoked by 1s light stimuli. In the presence of LAP4, paired-pulse stimulation caused depression of the Off-EPSC instead of facilitation. (paired-pulse ratio 0.48 ± 0.03). Paired-pulse stimulation also affected the decay and the latency of EPSCs. Conclusion: Paired-pulse stimulation differently affects the strength of synaptic transmission in On-and Off-pathways in retinal ganglion cells. The NMDA-receptor mediated component of the EPSC contributes importantly to PPF. Both pre- and postsynaptic mechanisms underlie PPF in retinal ganglion cells.
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