Fig. 7
Effect of Trem2R47H on age-dependent LTP deficit. a Time course of fEPSP slope (as percentage of baseline) following theta burst stimulation (TBS, white arrow at t = 20 min) of slices from 4-month-old WT, Trem2R47H, 5xFAD, and 5xFAD/Trem2R47H mice showing impaired LTP in 5xFAD but not 5xFAD/Trem2R47H. Insets show field synaptic responses collected during baseline (black line) and 1 h after TBS (red line). Scale: 1 mV/5 ms. b Mean potentiation (± SEM) during the last 10 min of recording in slices from 4-month-old mice shows reduction in 5xFAD but not 5xFAD/Trem2R47H mice. c Paired-pulse facilitation (PPF). At 4 months old, no significant difference was observed between groups at any of the three intervals tested. d Representative super-resolution images at 63X objective of CA1-SR from 4-month-old WT, Trem2R47H, 5xFAD, and 5xFAD/Trem2R47H mice immunolabeled with Bassoon for presynaptic elements (BSN, red) and PSD-95 for postsynaptic elements (green). e Quantification of Bassoon+ and PSD-95+ spots per µm3 showed a decrease in colocalized synaptic puncta in 5xFAD. f Time course of fEPSP slope following theta burst of slices from 12-month-old WT, Trem2R47H, 5xFAD, and 5xFAD/Trem2R47H mice show impaired LTP in Trem2R47H, 5xFAD and partial impairment in 5xFAD/Trem2R47H. g Mean potentiation (± SEM) during the last 10 min of recording in slices from 12-month-old mice shows reduction in Trem2R47H, 5xFAD, 5xFAD/Trem2R47H but a partial rescue in 5xFAD/Trem2R47H compared to 5xFAD. h Significant group effect was found in PPF at 40 ms (WT vs 5xFAD and WT vs 5xFAD/Trem2R47H; p = 0.0002, p < 0.0001 respectively) and 100 ms stimulus intervals (WT vs 5xFAD and WT vs 5xFAD/Trem2R47H; p = 0.0005, p = 0.0046 respectively). i. 63X representative super-resolution images of CA1-SR from 12-month-old WT, Trem2R47H, 5xFAD, and 5xFAD/Trem2R47H mice for Bassoon (red) and PSD-95 (green). j Quantification of Bassoon+ and PSD-95+ colocalization showed decrease in colocalized synaptic puncta in Trem2R47H and 5xFAD compared to WT with a trending increase in 5xFAD/Trem2R47H compared to 5xFAD. n = 5–6 mice/sex/genotype. LTP: n = 8–10 slices/sex/genotype. Data are represented as mean ± SEM. Two-way ANOVA followed by Tukey’s post hoc tests to examine biologically relevant interactions. Statistical significance is denoted by *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001