Contribution of glutamate transporter GLT-1 to removal of synaptically released glutamate in Purkinje cell synapses

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In this study, I aimed to clarify roles of glial glutamate transporter GLT-1 in glutamatergic synapses. The results are summarized as follows: 1. We compared the decay kinetics of excitatory postsynaptic currents (EPSCs) in cerebellar Purkinje cells (PCs) evoked by parallel fiber (CF) stimulation among wild-type (WT), GLAST (-/-) and GLT-1 (-/-) mice. The decay time constant of CF-EPSCs (τ_w) in GLT-1 (-/-) mice was slower than that in WT mice. However, the degree of this prolongation of τ_w was less prominent compared to that in GLAST (-/-) mice. 2. The values of τ_w in GLT-1 (-/-) mice and GLAST (-/-) mice were comparable to those estimated in WT mice in the presence of a potent blocker of glial glutamate transporters (2S,3S)-3- [3- (4-methoxybenzoylamino) benzyloxy] aspartate (PMB-TBOA) at 10 nM and 100 nM, which reduced the amplitudes of glutamate transporter currents elicited by CF stimulation in BG to ?81% and ?28%, respectively. We conclude that GLT-1 plays a minor role compared to GLAST in clearing synaptically released glutamate at CF-PC synapses. 3. Pharmacological blockage of glial glutamate transporter functions caused a spillover of synaptically released glutamate from a single CF terminal over to neighboring PCs, indicating that glial glutamate transporters are indispensable to maintain one-to-one relationship at CF-PC synapses by preventing glutamate spillover. 4. In hippocampal CA1 neurons of newborn rats in which the glutamate synapses are not formed yet, pharmacological blockage of glial glutamate transporters caused a spontaneous depolarizing oscillations mediated by activation of NMDA receptors, suggesting that glial transporters play a pivotal role in clearing non-synaptically released glutamate to maintain its extracellular concentration at a low level.