Synaptic Specializations Support Frequency-Independent Purkinje Cell Output from the Cerebellar Cortex

The output of the cerebellar cortex is conveyed to the deep cerebellar nuclei (DCN) by Purkinje cells (PCs). Here, we characterize the properties of the PC-DCN synapse in juvenile and adult mice and find that prolonged high-frequency stimulation leads to steady-state responses that become increasingly frequency independent within the physiological firing range of PCs in older animals, resulting in a linear relationship between charge transfer and activation frequency. We used a low-affinity antagonist to show that GABAA-receptor saturation occurs at this synapse but does not underlie frequency-invariant transmission. We propose that PC-DCN synapses have two components of release: one prominent early in trains and another specialized to maintain transmission during prolonged activation. Short-term facilitation offsets partial vesicle depletion to produce frequency-independent transmission. [Display omitted] •Steady-state transmission at PC-DCN synapses is frequency independent•GABAA-receptor saturation occurs but does not underlie frequency independence•Short-term facilitation is crucial to frequency invariance but is masked by depression•PC-DCN synapses are well described by a model with two distinct vesicle pools Turecek et al. show that, at synapses between Purkinje cells and deep cerebellar nuclear neurons, synaptic transmission is frequency invariant. This frequency invariance is generated by a balance between short-term depression and facilitation.