Constitutive deletion of Tyrobp normalizes altered synaptic plasticity and prevents defects in spatial learning behavior in 8-month-old APP/PSEN1 mice. a Electrode placement for field recordings of synaptic potentials. A bipolar stimulating electrode (“stim”) was positioned above the Schaffer collaterals in area CA3, 150–200 µm lateral to the recording electrode (Rec) in stratum radiatum of area CA1. b Basal input–output relationship for fEPSPs in 8-month-old WT (n = 8 mice; 23 recordings), Tyrobp−/− (n = 6 mice; 22 recordings), APP/PSEN1 (n = 5 mice; 16 recordings), and APP/PSEN1;Tyrobp−/− (n = 6 mice; 17 recordings) mice. Two-way ANOVA corrected for multiple comparisons (Tukey) was used for statistical comparisons. #p < 0.05; ###p < 0.001; ####p < 0.0001 in Tyrobp−/− vs. WT and Tyrobp−/− vs. APP/PSEN1. &p < 0.05 in APP/PSEN1;Tyrobp−/− vs. WT. $p < 0.05 in APP/PSEN1;Tyrobp−/− vs. Tyrobp−/−. c Left panel: paired-pulse facilitation (PPF) in 8-month-old WT (n = 8 mice; 24 recordings), Tyrobp−/− (n = 6 mice; 23 recordings), APP/PSEN1 (n = 5 mice; 18 recordings), and APP/PSEN1;Tyrobp−/− (n = 6 mice; 18 recordings) mice. Right panel: summary of PPF data. One-way ANOVA corrected for multiple comparisons (Tukey) was used for statistical comparisons. *p < 0.05, **p < 0.01; ***p < 0.001; ****p < 0.0001. d Synaptically induced long-term potentiation (LTP) in WT (n = 7 mice; 11 recordings), Tyrobp−/− (n = 6 mice; 12 recordings), APP/PSEN1 (n = 5 mice; 9 recordings), and APP/PSEN1;Tyrobp−/− (n = 6 mice; 9 recordings) mice. Two-way ANOVA corrected for multiple comparisons (Tukey) was used for statistical analysis over the final 5 min of recordings. e 3,5-dihydroxyphenylglyine (DHPG) induced long-term depression (LTD) in WT (n = 5 mice; 8 recordings), Tyrobp−/− (n = 6 mice; 11 recordings), APP/PSEN1 (n = 5 mice; 10 recordings), and APP/PSEN1;Tyrobp−/− (n = 5 mice; 9 recordings) mice. Two-way ANOVA corrected for multiple comparisons (Tukey) was used for statistical analysis over the final 5 min of recordings. *p < 0.05. Data presented as mean ± SEM. f Spatial learning behavior in the Barnes Maze test in 8-month-old APP/PSEN1 mice. Four groups of 8-month-old mice were used: WT (n = 9), Tyrobp−/− (n = 12), APP/PSEN1 (n = 17), or APP/PSEN1;Tyrobp−/− (n = 6). g Percentage of distance traveled in the target quadrant (TQ). h Latency (in seconds) to find the hidden zone. One-way ANOVA on the day 4 was used for statistical comparisons, *p < 0.05 in APP/PSEN1 vs. WT; $p < 0.05 in APP/PSEN1 vs. APP/PSEN1;Tyrobp−/−;
#p < 0.01 in APP/PSEN1 vs. Tyrobp−/−. Data presented as mean ± SEM