(A) The input-output slope is significantly increased in Trem2R47H/R47H rats [two-way ANOVA, stimulation intensity x genotype interaction F(6, 144)=6.745, p<0.0001****; post-hoc Sidak's multiple comparisons test: 1.2 mV p=0.0175*; 1.4 mV: p=0.0021**; 1.6 mV: p=0.0001***] Representative traces of fEPSPs in response to increasing stimulus from 0.4 to 1.6 mA are shown on the top. (B) LTP is impaired in Trem2R47H/R47H rats. Average traces of the baseline and the last 5mins of LTP are shown on top. (C) Plot of fEPSP slope change of the last 10 min of LTP in B (unpaired t test, p<0.0001****). (D) The increase of input-out slope in Trem2R47H/R47H rats is reversed by application of anti-TNF-α [ANOVA for repeated measures F(18, 300)=6.579, p<0.0001****; post-hoc Tukey's multiple comparisons test: 0.8 mV RH/RH + Isotype vs. w/w + anti-TNF-α p=0.0479*; 1.0 mV RH/RH + Isotype vs. RH/RH + anti-TNF-α p=0.0061**, RH/RH + Isotype vs. w/w + anti-TNFα p=0.0072**, RH/RH + Isotype vs. w/w + Isotype p=0.0113*; 1.2 mV RH/RH + Isotype vs. RH/RH + anti-TNFα p=0.0009***, RH/RH + Isotype vs. w/w + anti-TNF-α p=0.0009***, RH/RH + Isotype vs. w/w + Isotype p=0.0029**; 1.4 mV RH/RH + Isotype vs. RH/RH + anti-TNF-α p<0.0001****, RH/RH + Isotype vs. w/w + anti-TNF-α p<0.0001****, RH/RH + Isotype vs. w/w + Isotype p=P < 0.0001****; 1.6 mV RH/RH + Isotype vs. RH/RH + anti-TNF-α p<0.0001****, RH/RH + Isotype vs. w/w + anti-TNF-α P p<0.0001****, RH/RH + Isotype vs. w/w + Isotype p<0.0001****]. Representative fEPSP traces are shown on top. (E) The impaired LTP is restored by application of anti-TNF-α antibody. The average traces of the baseline and the last 5mins of LTP are shown on top. (F) Plot of fEPSP slope change of the last 10 min of LTP in E [one-way ANOVA, F(3, 36)=1490, p<0.0001; post-hoc Tukey's multiple comparisons test: RH/RH + Isotype vs. RH/RH + anti-TNF-α p<0.0001****, RH/RH + Isotype vs. w/w + anti-TNF-α P p<0.0001****, RH/RH + Isotype vs. w/w + Isotype p<0.0001****].