Ca(2+) current facilitation determines short-term facilitation at inhibitory synapses between cerebellar Purkinje cells.

KEY POINTS: Short-term facilitation takes place at GABAergic synapses between cerebellar Purkinje cells (PCs). By directly patch clamp recording from a PC axon terminal, we studied the mechanism of short-term facilitation. We show that the Ca(2+) currents elicited by high-frequency action potentials were augmented in a [Ca(2+) ]i -dependent manner. 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. 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.