Figure 1.

Rescue of hyperexcitability in Fmr1^KO mice by genetic manipulation of APP. Thalamocortical slices from WT (n = 17), Fmr1^KO (n = 22), App^HET (n = 13), and Fmr1^KO/App^HET (n = 13) male mice were assessed for neocortical hyperexcitability. (A) Trace recordings and (B) histogram depicting a significant increase in UP state activity in Fmr1^KO slices compared to WT, which was completely rescued in the Fmr1^KO/App^HET. Error bars represent SEM. Horizontal bars denote statistically different levels by one-way ANOVA and Bonferroni's multiple comparison test (P < 0.0001). DHPG-induced prolonged epileptiform discharges were assessed in hippocampal slices from Fmr1^KO and Fmr1^KO/App^HET male mice (n = 6 mice per cohort). The recordings were continuous for 3 or more hours in a single slice per animal. (C) Summary frequency histogram of synchronized epileptiform discharges from Fmr1^KO and Fmr1^KO/App^HET slices in the presence of DHPG (60 min) and after DHPG washout at the indicated times up to 2 h. The mean durations of epileptiform discharges in Fmr1^KO/App^HET slices at 30, 60, 90, and 120 min after DHPG washout are significantly shorter than those in Fmr1^KO for all times tested (P < 0.001).