Fig. 4. Lovastatin prevents the emergence of plasticity deficits associated with the loss of FMRP.

(A) Left: Time course plotting field excitatory postsynaptic potential (fEPSP) slopes normalized to baseline after LTP induction in layers 2 to 5 synapses in the prelimbic mPFC taken from 4- to 6-week-old WT and Fmr1 KO rats. Right: Averages of fEPSP slopes normalized to baseline during the last 20 min of the recording (70 to 90 min). (B) Left: Time course plotting fEPSP slopes normalized to baseline after LTP induction at synapses from layer 2/3 inputs onto layer 5 neurons in the prelimbic mPFC taken from 10- to 12-week-old WT and Fmr1 KO rats. Right: Averages of fEPSP slopes normalized to baseline during the last 20 min of the recording (70 to 90 min). (C) Left: Experimental time course for assessment of the effect of lovastatin (lova) treatment beginning at 5 weeks of age on WT and Fmr1 KO plasticity in the prelimbic mPFC. Middle: Time course plotting averages of fEPSP slopes normalized to baseline after LTP induction in layers 2 to 5 synapses in prelimbic mPFC slices taken from 10- to 12-week-old WT and Fmr1 KO treated with either control or lovastatin diet. Right: Averages of fEPSP slopes normalized to baseline during the last 20 min of recordings (70 to 90 min). Insets: Example traces showing synaptic responses during baseline (black trace) and at 80 to 90 min (gray trace). Scale bar, 0.5 mV; 5 ms. Sample sizes: LTP 4 to 6 weeks, n = 6 for WT and KO; LTP 10 to 12 weeks, n = 7 for WT and KO; for lovastatin effects on LTP, n_WTcontrol = 9, n_WTlova = 7, n_KOcontrol = 9, n_KOlova = 8; *P < 0.05; **P < 0.01 difference between groups; two-way ANOVA with post hoc two-sample t tests was used for data analyses (for details, see table S6, G and H). P values for post hoc two-sample t tests have been controlled for the false discovery rate using the Benjamini-Hochberg procedure.