Recurrent axon collaterals underlie facilitating synapses between cerebellar Purkinje cells

Abstract

Morphological studies have provided ample evidence for synaptic connections between cerebellar Purkinje cells (PCs), but the functional properties of these synapses remain elusive. We report on direct recordings of synaptically connected PCs in mice cerebellar slices. In PCs filled with a fluorescent dye to aid axon visualization and postsynaptic target identification, presynaptic action potentials elicited unitary inhibitory postsynaptic currents in neighboring PCs in 10% of potential connections tested. In 11 pairs, postsynaptic currents had a delay onset of 1.62 +/- 0.16 ms with respect to the presynaptic spike, a 10-90% rise time of 2.20 +/- 0.33 ms, and a monoexponential decay with a time constant of 13.3 +/- 1.7 ms. Average values for peak current and variance-to-mean ratio were 55 +/- 14 and 30 +/- 3 pA, respectively. In contrast to the depressing nature of the synapse between PCs and deep cerebellar nuclei neurons, PC-PC synapses exhibited strong facilitation operating within a time window of a few milliseconds; paired-pulse ratios for 3- and 20-ms intervals were 1.79 +/- 0.18 and 1.01 +/- 0.14, respectively (n = 6). The facilitation is of presynaptic nature because it is accompanied by a decrease in failure rate. Trains of action potentials evoked in presynaptic varicosities volume-averaged calcium transients whose peak increased 1.7-fold as the frequency increased from 50 to 166 Hz. We suggest that PC-PC synapses are tuned for high fidelity of transmission during bursts of PC activity and that their operation in the cerebellar circuit modulates synchronized PC firing.