Key pointsr Short-term facilitation takes place at GABAergic synapses between cerebellar Purkinje cells (PCs).r By directly patch clamp recording from a PC axon terminal, we studied the mechanism of short-term facilitation.r We show that the Ca 2+ currents elicited by high-frequency action potentials were augmented in a [Ca 2+ ] i -dependent manner.r The facilitation of synaptic transmission showed 4-5th power dependence on the Ca 2+ current facilitation, and was abolished when the Ca 2+ current amplitude was adjusted to be identical.r Short-term facilitation of Ca 2+ currents predominantly mediates short-term facilitation at synapses between PCs.Abstract Short-term synaptic facilitation is critical for information processing of neuronal circuits. Several Ca 2+ -dependent positive regulations of transmitter release have been suggested as candidate mechanisms underlying facilitation. However, the small sizes of presynaptic terminals have hindered the biophysical study of short-term facilitation. In the present study, by directly recording from the axon terminal of a rat cerebellar Purkinje cell (PC) in culture, we demonstrate a crucial role of [Ca 2+ ] i -dependent facilitation of Ca 2+ currents in short-term facilitation at inhibitory PC-PC synapses. Voltage clamp recording was performed from a PC axon terminal visualized by enhanced green fluorescent protein, and the Ca 2+ currents elicited by the voltage command consisting of action potential waveforms were recorded. The amplitude of presynaptic Ca 2+ current was augmented upon high-frequency paired-pulse stimulation in a [Ca 2+ ] i -dependent manner, leading to paired-pulse facilitation of Ca 2+ currents. Paired recordings from a presynaptic PC axon terminal and a postsynaptic PC soma demonstrated that the paired-pulse facilitation of inhibitory synaptic transmission between PCs showed 4-5th power dependence on that of Ca 2+ currents, and was completely abolished when the Ca 2+ current amplitude was adjusted to be identical. Thus, short-term facilitation of Ca 2+ currents predominantly mediates short-term synaptic facilitation at synapses between PCs.
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