Glutamate transporters contribute to the time course of synaptic transmission in cerebellar granule cells

Transporters are thought to assist in the termination of synaptic transmiss ion at some synapses by removing neurotransmitter from the synapse. To inve stigate the role of glutamate transport in shaping the time course of excit atory transmission at the mossy fiber-granule cell synapse, the effects of transport impairment were studied using whole-cell voltage- and current-cla mp recordings in slices of rat cerebellum. Impairment of transport by L-tra ns-pyrrolidine-2,4-dicarboxylate (PDC) produced a prolongation of the decay of the AMPA receptor-mediated current after a repetitive stimulus, as well as prolongation of single stimulus-evoked EPSCs when AMPA receptor desensi tization was blocked. PDC also produced a prolongation of both single and r epetitive-evoked NMDA receptor-mediated EPSCs. Enzymatic degradation of ext racellular glutamate did not reverse the PDC-induced prolongation of AMPA r eceptor-mediated current after a repetitive stimulus, suggesting that trans porter binding sites participate in limiting glutamate spillover. In curren t-clamp recordings, PDC dramatically increased the total area of the EPSP a nd the burst duration evoked by single and repetitive stimuli. These data i ndicate that glutamate transporters play a significant role in sculpting th e time course of synaptic transmission at granule cell synapses, most likel y by limiting the extent of glutamate spillover. The contribution of transp orters is particularly striking during repetitive stimulus trains at physio logically relevant frequencies. Hence, the structural arrangement of the gl omerulus may enhance the contribution of transporters to information proces sing by limiting the extent of glutamate spillover between adjacent synapse s.