Feed-forward inhibition shapes the spike output of cerebellar Purkinje cells.

Although the cerebellum is thought to play a key role in timing of movements on the time scale of milliseconds, it is unclear how such temporal fidelity is ensured at the cellular level. We have investigated the timing of feed-forward inhibition onto interneurons and Purkinje cells activated by parallel fibre stimulation in slices of cerebellar cortex from P18-25 rats. Feed-forward inhibition was activated within approximately 1 ms after the onset of excitation in both cell types. The rapid onset of feed-forward inhibition sharply curtailed EPSPs and increased the precision of the resulting action potentials. The time window for summation of EPSPs was reduced to 1-2 ms in the presence of feed-forward inhibition, which could inhibit the efficacy of asynchronous EPSPs for up to 30 ms. Our findings demonstrate how the inhibitory microcircuitry of the cerebellar cortex orchestrates synaptic integration and precise timing of spikes in Purkinje cells, enabling them to act as coincidence detectors of parallel fibre input.