Ca2+ Current Facilitation Determines Short-Term Facilitation At Inhibitory Synapses Between Cerebellar Purkinje Cells

Short-term synaptic facilitation is critical for information processing of neuronal circuits. Several Ca2+-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 [Ca2+](i)-dependent facilitation of Ca2+ 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 Ca2+ currents elicited by the voltage command consisting of action potential waveforms were recorded. The amplitude of presynaptic Ca2+ current was augmented upon high-frequency paired-pulse stimulation in a [Ca2+](i)-dependent manner, leading to paired-pulse facilitation of Ca2+ 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 Ca2+ currents, and was completely abolished when the Ca2+ current amplitude was adjusted to be identical. Thus, short-term facilitation of Ca2+ currents predominantly mediates short-term synaptic facilitation at synapses between PCs.