AMPA receptor kinetics limit retinal amacrine cell excitatory synaptic responses

Amacrine cells that respond transiently to maintained illumination are thou ght to mediate transient inhibitory input to ganglion cells. The excitation of these transient amacrine cells is thought to be limited by inhibitory f eedback to bipolar cells. We investigated the possibility that desensitizin g AMPA and/or kainate (KA) receptors on amacrine cells might also limit the duration of amacrine cell excitation. To determine how these receptors mig ht affect amacrine cell input and output, we made whole-cell recordings fro m amacrine and ganglion cells in the salamander retinal slice. The specific AMPA receptor antagonist GYKI-53655 blocked non-NMDA receptor-mediated ama crine cell excitatory postsynaptic currents (EPSCs) and kainate puff-elicit ed currents, indicating that AMPA, and not KA, receptors mediated the respo nses. Cyclothiazide, an agent that reduces AMPA receptor desensitization, i ncreased the amplitude and duration of amacrine cell EPSCs. To measure the output of transient amacrine cells, we recorded glycinergic inhibitory post synaptic currents (IPSCs) from ganglion cells, and found that these were al so enhanced by cyclothiazide. Thus, prolongation of amacrine cell AMPA rece ptor activation enhanced amacrine cell output. Current responses elicited b y puffing glycine onto ganglion cell dendrites were not affected by cycloth iazide, indicating that the enhancement of glycinergic IPSCs was not due to a direct effect on glycine receptors. These data suggest that rapid AMPA r eceptor desensitization and/or deactivation limits glycinergic amacrine cel l excitation and the resulting inhibitory synaptic output.