Complex spike clusters and false-positive rejection in a cerebellar supervised learning rule

Heather K. Titley, Mikhail Kislin, Dana H. Simmons, Samuel S.H. Wang, Christian Hansel

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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 [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, 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.

Original languageEnglish (US)
Pages (from-to)4387-4406
Number of pages20
JournalJournal of Physiology
Issue number16
StatePublished - 2019

All Science Journal Classification (ASJC) codes

  • Physiology


  • Complex spikes
  • cerebellum
  • long-term depression
  • signal-to-noise ratio


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