Pre- and postsynaptic determinants of EPSC waveform at cerebellar climbing fiber and parallel fiber to Purkinje cell synapses.

Excitatory postsynaptic currents (EPSCs) at the parallel fiber and climbing fiber to Purkinje cell synapses were studied by whole-cell clamping Purkinje cells in cerebellar slices. Reducing glutamate release with adenosine or GABA decreased the amplitude of the EPSCs, with a larger suppression being produced at the parallel fiber synapse. Reducing glutamate release also speeded the decay of the EPSCs, and this effect was not a series resistance artefact since postsynaptic reduction of the current with CNQX did not speed the EPSC decay. Blocking glutamate uptake slowed the decay of the EPSCs. At the climbing fiber synapse, adenosine had little suppressive effect on the smaller EPSC evoked by the second of a pair of stimuli. Blocking desensitization of postsynaptic AMPA receptors prolonged the EPSC decay, preferentially increased the size of the second EPSC, and resulted in adenosine having a similar suppressive effect on the first and second EPSC. These data suggest that, at these synapses, the fall of glutamate concentration in the synaptic cleft overlaps with the decay of the EPSC, and that the EPSC size and duration are controlled by the amount of glutamate released, the rate of glutamate uptake, and desensitization.