Complex spike clusters and false‐positive rejection in a cerebellar supervised learning rule. (26th July 2019) - Titley, Heather K.
Abstract : 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 parallel fibre long‐term depression. Doublet stimulation is required to induce long‐term depression with an optimal parallel‐fibre to first‐complex‐spike timing interval of 150 ms. Abstract: The classic example of biological supervised learning occurs at cerebellar parallel fibre (PF) to Purkinje cell synapses, comprising the most abundant synapse in the mammalian brain. Long‐term depression (LTD) at these synapses is driven by climbing fibres (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 [Ca 2+ ]o and [Mg 2+ ]o concentrations in slices, we determined that complex‐spike doublets delivered 100–150 ms after PF stimulus onset were required to trigger PF‐LTD, which is consistent with the 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. 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 parallel fibre long‐term depression. Doublet stimulation is required to induce long‐term depression with an optimal parallel‐fibre to first‐complex‐spike timing interval of 150 ms.