Glutamate uptake limits synaptic excitation of retinal ganglion cells.

EPSCs of retinal ganglion cells decay more slowly than do those of most other CNS neurons, in part because of the long time course of glutamate release from bipolar cells. Here we investigated how glutamate clearance and AMPA receptor desensitization affect ganglion cell EPSCs in the salamander retinal slice preparation. Inhibition of glutamate uptake greatly prolonged ganglion cell EPSCs evoked by light or monosynaptic electrical stimuli but had little effect on spontaneous miniature EPSCs (mEPSCs). This suggests that single quanta of glutamate are cleared rapidly by diffusion but multiple quanta can interact to lengthen the postsynaptic response. Some interaction between quanta is likely to occur even when glutamate uptake is not inhibited. This seems to depend on quantal content, because reducing glutamate release with low Ca2+, paired-pulse depression, or weak stimuli shortened the EPSC decay. High quantal content glutamate release may lead to desensitization of postsynaptic receptors. We reduced the extent of AMPA receptor desensitization by holding ganglion cells at positive potentials. This increased the amplitude of the late phase of evoked EPSCs but did not affect the decay rate after the first 50 msec of the response. In contrast, the holding potential had little effect on mEPSC kinetics. Our results suggest that desensitization limits the late phase of AMPA receptor-mediated EPSCs, whereas glutamate uptake controls the duration of both AMPA and NMDA receptor-mediated responses.