Fig. 3

Differential expression of synaptic proteins in the cerebellar cortex and reduction of facilitation at the Purkinje cell - parallel fiber synapse in cuprizone-fed mice. a Volcano plot of proteomic analysis of the cerebellar cortex of wild type naive and cuprizone fed mice (CUP5W), depicting individual proteins and their regulation status in CUP5W as downregulated (blue), upregulated (red) and not differentially regulated (grey). Individual names are plotted for selected proteins (n = 3 independent samples per group). b. Up- (top) and down- (bottom) regulated gene sets from GO_Biological_process_2021 sets in WT mice after treatment with cuprizone. For clarity, gene sets containing the term “RNA” were filtered out, and up to 10 most significant gene sets are shown. The complete list can be found in supplementary Table 1. c. Heatmap representation of proteomic analysis showing differential expression of proteins related to glutamatergic synaptic transmission, showing an overall reduced relative expression in CUP5W. d Schematic representation of the PF-PC synapse. Parallel fibers are stimulated with an extracellular electrode (red) and EPSCs are recorded on PC using whole-cell patch clamp (blue arrow). e Relative amplitude of 2nd to 1st EPSC showing a reduction in CUP5W facilitation with time of cuprizone feeding. Each point represents an individual cell. Whiskers represent mean ± SEM, P values were obtained after unpaired t-test. Asterisks represent significant p-values (*p < 0.05, **p < 0.01, ***p < 0.001, **** p < 0.0001). f Representative excitatory post-synaptic current (EPSC) traces of naive (grey, top panel) and CUP5W (pink, bottom panel) animals upon stimulation of parallel fibers at 50 Hz