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

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 [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.

Sushi domain-containing protein 4 controls synaptic plasticity and motor learning

“…In slices from Susd4 WT mice, tetanic stimulation every 3 s during 5 min induced only a transient increase in transmission of about 20% and the amplitude of the response returned to baseline after only 15 min ( Figure 2E and Figure 2—figure supplement 1 ). This result suggests that under our experimental conditions and in this particular genetic background, LTD might be favored in contrast to previously obtained results ( Binda et al, 2016 ; Titley et al, 2019 ). In the case of Susd4 KO PCs, the same protocol induced LTP with a 27% increase in transmission that was maintained after 35 min ( Figure 2E ).…”

“…Representative traces of the CF-EPSP are shown. The quantification of the number of spikelets (spikes induced by repeated CF stimulation [ Mathy et al, 2009 ; Titley et al, 2019 ]) did not reveal any difference between WT and KO PCs (unpaired Student’s t-test, p=0.5791). Bottom: Measurements of the CF-EPSP area and hyperpolarization area during the LTD induction protocol.…”

Cellular-resolution mapping uncovers spatial adaptive filtering at the rat cerebellum input stage

“…These channels can differentiate the cerebellar cortex filtering properties 53 , 54 , focus the signal in vertical beams traveling towards the molecular layer (see refs. 11 , 33 , 55 ) and control signal integration and coincidence detection in Purkinje cells 56 , 57 . Thus, plasticity-controlled distribution of spike timing and discharge can remarkably impact mutual information transfer at the cerebellum input stage 58 , 59 and influence subsequent computations in the molecular layer and Purkinje cells.…”

Climbing Fibers Provide Graded Error Signals in Cerebellar Learning

“…Importantly, Purkinje cell dendrites can integrate this burst firing into a graded Ca 2+ response. In addition, complex-spike doublets have been also shown to increase Ca 2+ influx compared with single complex spikes and have been suggested to be “instruction” signals compared to spontaneous “noise” single complex spikes (Titley et al, 2019).…”