Heterozygous Clptm1 KO interferes with excitatory synaptic plasticity without changing basal excitatory transmission. A, mEPSC recordings were collected from CA1 pyramidal neurons at P16–17. No differences were detected in mEPSC amplitude or frequency. WT, n = 19 cells from two mice; KOfirst/+, n = 22 cells from four mice; for cumulative probability of interevent interval, p = 0.3818, K-S test; for cumulative probability of amplitude, p = 0.1644, K-S test; for frequency, p = 0.6201, t test; for amplitude, p = 0.6417, t test. B, eEPSCs were recorded from CA1 pyramidal cells while stimulating Schaffer collateral fibers with increasing multiples of threshold intensity at P15–18. No differences were detected in eEPSC input/output relationship. WT, n = 10 cells from four mice; KOfirst/+, n = 11 cells from two mice; stimulation intensity p < 0.0001; genotype p = 0.9605; stimulation intensity and genotype interaction p > 0.9999, two-way ANOVA. C, No differences were detected in paired-pulse ratio of eEPSCs recorded from CA1 pyramidal cells with multiple interpulse intervals at P15–18. WT, n = 12 cells from four mice; KOfirst/+, n = 12 cells from two mice; interpulse interval p < 0.0001; genotype p = 0.6656; interpulse interval and genotype interaction p = 0.9857, two-way ANOVA. D, No differences were detected in input/output relationship of the slope of the CA1 fEPSP in response to increasing stimulation of the Schaffer collateral fibers at P15–16. WT, n = 11 slices from five mice; KOfirst/+, n = 14 slices from six mice; stimulation intensity p < 0.0001; genotype p = 0.1017; stimulation intensity and genotype interaction p = 0.9340, two-way ANOVA. E, LTP was induced by HFS (1 s, 100 Hz) of Schaffer collateral fibers after obtaining 20 min stable baseline recordings. Bar graphs of the slope of the fEPSP recorded 0–2 and 55–60 min after HFS show that heterozygous Clptm1 KOfirst mice were deficient in the induction and expression of LTP. WT, n = 5 slices from five mice; KOfirst/+, n = 5 slices from three mice; *p < 0.05, Mann–Whitney test.