J Physiol. 2019 Jul 11.
KEY POINTS: Spike doublets comprise ∼10% of in vivo complex spike events under spontaneous conditions and ∼20% (up to 50%) under evoked conditions Under near-physiological slice conditions single complex spikes do not induce LTD Doublet stimulation is required to induce parallel fiber LTD with an optimal parallel fiber-to-first complex spike timing interval of 150 ms ABSTRACT: The classic example of biological supervised learning occurs at cerebellar parallel fiber (PF) to Purkinje cell synapses, the most abundant synapse in the mammalian brain. Long-term depression (LTD) at these synapses is driven by climbing fibers (CFs), which fire continuously about once per second, and therefore generate potential false-positive events. We show that pairs of complex spikes are required to induce LTD. In vivo, sensory stimuli evoked complex-spike doublets with intervals ≤ 150 ms in up to 50% of events. Using realistic [Ca2+ ]o and [Mg2+ ]o concentrations in slices, we determined that complex-spike doublets delivered 100-150 ms after PF stimulus onset were required to trigger PF-LTD, consistent with requirements for eyeblink conditioning. Inter-complex spike intervals of 50-150 ms provided optimal decoding. This stimulus pattern prolonged evoked spine calcium signals and promoted CaMKII activation. Doublet activity may provide a means for CF instructive signals to stand out from background firing. This article is protected by copyright. All rights reserved.