Fig. 3

Trem2 deletion aggravates memory and synaptic impairment associated with AAV-tau expression. A-B Trem2 deletion aggravates tau-mediated spatial memory impairment. WT or Trem2 KO animals were stereotactically injected with AAV control (AAV9-synapsin GFP) or AAV-tau constructs into the MEC region at 4 months of age, and subjected to 5 days of navigational training using the Barnes land maze (A); training of a cohort 5-weeks following AAV injection is shown. B 2 days following last training, spatial memory was evaluated by probe test in cohorts 2 weeks (left graph, n = 6 animals per genotype/treatment) or 5 weeks (right graph, WT/AAV con – n = 10; Trem2 KO/con – n = 10; WT/AAV tau – n = 9; Trem2 KO/AAV-tau – n = 8 animals) after AAV injection. Representative traces of motion tracks for WT and Trem2 KO animals 5 weeks after AAV injection are shown; red circle indicates the target hole (traces, right panel). C-D Trem2 deletion aggravates tau-mediated contextual fear memory impairment. WT or Trem2 KO animals were stereotactically injected with AAV control or AAV-tau constructs as in (A), and characterized for freezing time during pre-conditioning 5 weeks after AAV injection (C), and in fear conditioning probe tests 2 weeks (top, n = 6 animals per genotype/treatment) or 5 weeks (bottom, WT/AAV con – n = 10; Trem2 KO/con – n = 10; WT/AAV tau – n = 9; Trem2 KO/tau – n = 8 animals) after AAV injection (D). E Population spike amplitude recorded in the DG region from acute hippocampal slices in WT and Trem2 KO animals 5 weeks following AAV injection; population spike amplitudes are shown (WT control, 12 slices from n = 4 animals; WT AAV-tau, 13 slices from n = 4 animals; Trem2 KO control, 15 slices from n = 5 animals; Trem2 KO AAV-tau, 15 slices from n = 5 animals). Representative traces on the left depict depolarizing spikes following stimulation in WT and Trem2 KO hippocampus as indicated. Graphs depict mean ± SE (error bars in (E) represent SE from total slice recordings from each experimental group), statistical significance was determined using One-way ANOVA with Dunn’s multiple comparison (D) and Two-way ANOVA (B, E) (*p < 0.05, **p < 0.01). F Representative histological images in MEC and DG brain regions stained for human tau (T13, green), PSD95 (red), Iba1 (purple) and nuclei (DAPI, blue) in WT and Trem2 KO mouse brain 5 weeks following AAV-tau injection. Bar = 50 μm. G Quantification of PSD95 particles in DG from WT and Trem2 KO brain (n = 8 animal/genotype) in (F); graphs represent mean ± SE. Statistical significance was determined using unpaired Student’s t-tests (***p < 0.001)