Efficacy and short-term plasticity at GABAergic synapses between Purkinje and cerebellar nuclei neurons.

Although the entire output of the cerebellar cortex is conveyed to the deep cerebellar nuclei neurons (DCNs) via the GABAergic synapses established by Purkinje cells (PCs), very little is known about the strength and dynamic properties of PC-DCN connections. Here we show that activation of PC-DCN unitary connections induced large conductance changes (11.7 nS) in DCNs recorded in whole cell patch configuration in acute slices, suggesting that activity of single PCs might significantly affect the output of its target neurons. Based on the large unitary quantal content (18) inferred from calculations of PC-DCN quantal size (0.65 nS) and the near absence of failures in synaptic transmission during control conditions, we conclude that PC-DCN connections are highly multi-sited. The analysis of dynamic properties of PC-DCN synapses demonstrated remarkable paired pulse depression (PPD), maximal at short intervals (paired pulse ratio of 0.15 at 7-ms interval). We provide evidence that PPD is presynaptic in origin and release-independent. In addition, multiple pulse stimulation revealed that PC-DCN synapses exhibited larger sensitivity to dynamic than to steady signals. We postulate that the, otherwise paradoxical, combination of marked short-term depression with strong multi-sited connections is optimal to transfer dynamic information at unitary level by performing spatial average of release probability across the numerous release sites. This feature could enable these synapses to encode presynaptic time-varying signals of single PCs as moment-to-moment changes in synaptic strength, a capacity well suited to the postulated role of cerebellum in control of temporal aspects of motor or cognitive behaviors.