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. 2023 Feb 17;18:12. doi: 10.1186/s13024-023-00598-4

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© The Author(s) 2023

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 7 — Effect of Trem2^R47H 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, Trem2^R47H, 5xFAD, and 5xFAD/Trem2^R47H mice showing impaired LTP in 5xFAD but not 5xFAD/Trem2^R47H. 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/Trem2^R47H 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, Trem2^R47H, 5xFAD, and 5xFAD/Trem2^R47H 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, Trem2^R47H, 5xFAD, and 5xFAD/Trem2^R47H mice show impaired LTP in Trem2^R47H, 5xFAD and partial impairment in 5xFAD/Trem2^R47H. g Mean potentiation (± SEM) during the last 10 min of recording in slices from 12-month-old mice shows reduction in Trem2^R47H, 5xFAD, 5xFAD/Trem2^R47H but a partial rescue in 5xFAD/Trem2^R47H compared to 5xFAD. h Significant group effect was found in PPF at 40 ms (WT vs 5xFAD and WT vs 5xFAD/Trem2^R47H; p = 0.0002, p < 0.0001 respectively) and 100 ms stimulus intervals (WT vs 5xFAD and WT vs 5xFAD/Trem2^R47H; p = 0.0005, p = 0.0046 respectively). i. 63X representative super-resolution images of CA1-SR from 12-month-old WT, Trem2^R47H, 5xFAD, and 5xFAD/Trem2^R47H mice for Bassoon (red) and PSD-95 (green). j Quantification of Bassoon⁺ and PSD-95⁺ colocalization showed decrease in colocalized synaptic puncta in Trem2^R47H and 5xFAD compared to WT with a trending increase in 5xFAD/Trem2^R47H 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