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 ] and [Mg ] 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.
}, year = {2019}, journal = {The Journal of physiology}, volume = {597}, pages = {4387-4406}, month = {12/2019}, issn = {1469-7793}, doi = {10.1113/JP278502}, language = {eng}, }