DESENSITIZING GLUTAMATE RECEPTORS SHAPE EXCITATORY SYNAPTIC INPUTS TOTIGER SALAMANDER RETINAL GANGLION-CELLS

AMPA/kainate (KA) receptors mediate a component of ganglion cell excit atory postsynaptic currents (EPSCs). We investigated whether desensiti zation at these receptors contribute to the shape of transient EPSCs i n ON-OFF ganglion cells. Whole-cell, voltage-clamp recordings were mad e from ganglion cells in the retinal slice or in isolation. EPSCs were evoked by either stimulating the slice with light or puffing K+ at th e outer plexiform layer (OPL). The AMPA/KA receptor-mediated component of the EPSCs was isolated by including NMDA receptor antagonists in t he bath, Strychnine and picrotoxin blocked inhibitory inputs. In isola ted ganglion cells, cyclothiazide (10 mu M), which blocks desensitizat ion in non-NMDA receptors, enhanced both the amplitude and the duratio n of currents evoked by puffs of AMPA or glutamate. EPSCs evoked by K-puffs in the OPL were also enhanced by cyclothiazide (30 mu M). When AMPA/KA receptors were blocked with NBQX (10 mu M), no enhancement of the EPSCs by cyclothiazide was observed, indicating that cyclothiazide did not act presynaptically. Cyclothiazide also enhanced the amplitud e and duration of both the ON and OFF light-evoked (L-) EPSCs recorded in ON-OFF ganglion cells. Current-voltage relationships showed the en hancement was not voltage dependent. When control and enhanced respons es where normalized, it was observed that the rate of desensitization of both the ON and OFF L-EPSCs was decreased by cyclothiazide. Cycloth iazide selectively enhanced the AMPA/ KA receptor-mediated component o f ganglion cells EPSCs, suggesting that desensitization of AMPA/KA rec eptors shape transient L-EPSCs.