Figure 6.

Disruption of mGlu5-Homer interactions is sufficient to mimic neocortical hyperexcitability and audiogenic seizures observed in Fmr1 KO mice. A, B, The mGlu5F>R mutation dose-dependently increases spontaneous UP state duration. A, Representative extracellular multiunit recordings of spontaneous, persistent activity or UP states from layer 4 of acute somatosensory neocortical slices from each genotype. Calibration: 50 μV, 1 s. B, Group data of average UP state duration in WT, Het, and mGlu5^R/R littermates (WT, n = 29 slices; Het, n = 14; mGlu5^R/R, n = 18; ANOVA; Tukey post hoc). C, The average amplitude (normalized to baseline) of UP states is increased in mGlu5^R/R, but UP states occur less frequently (ANOVA; Tukey post hoc). D, The mGlu5F>R mutation increases the incidence and severity of audiogenic seizures as assessed by seizures score and by percentage mice that seized (described in Materials and Methods) (N = 27, N = 28, and N = 21 for WT, Het, and mGlu5^R/R littermates, respectively). Score: ANOVA; Tukey multiple-comparison test; percentage seized: Fisher's exact test. *p < 0.05. **p < 0.01. ***p < 0.001.