Figure 3. Potentiation is prematurely restricted in CA2 of a mouse model of RTT via PNNs.

(A) Potentiation failed to be induced at CA2 stratum radiatum synapses at ages P8–11 in acute hippocampal slices from Mecp2-null mice (red) compared with WT (black). Top: Representative EPSCs from Mecp2-null P8–11 CA2 neurons at baseline and 20 minutes after the LTP pairing protocol (post-stimulation). Right: Normalized mean response amplitudes 18–20 minutes after pairing; **P = 0.0031, 2-tailed unpaired t test (n = 14 and 13, WT littermate and Mecp2-null, respectively). (B) EPSC amplitudes in response to indicated stimulation current intensity were not different in Mecp2-null CA2 neurons compared with WT littermate at P8–11; main effect of genotype P = 0.2738, 2-way ANOVA, repeated-measures analysis, Šidák’s post hoc test (n = 9 and 5, WT littermate and Mecp2-null, respectively). Top: Representative traces from a Mecp2-null CA2 neuron at P8 in response to increasing stimulation intensities. (C) Paired-pulse ratio did not differ between Mecp2-null and WT CA2 synapses (S1, peak of first stimulus response; S2, peak of second stimulus response). Top: Representative traces using a 50-millisecond stimulus interval from a P11 Mecp2-null CA2 neuron; average of 4 responses. (D) Action potential firing frequency of Mecp2-null CA2 neurons did not differ in comparison with WT; P > 0.05, 2-way ANOVA (n = 12 and 18, WT and Mecp2-null, respectively). Top: Representative traces of action potentials from 0 to 180 pA current injection in a P8 Mecp2-null CA2 cell. (E) Degradation of PNNs by incubation of slices in vitro with chondroitinase ABC (ChABC) for 2 hours resulted in potentiation being restored. Top: Representative EPSCs from CA2 +ChABC Mecp2-null P8 neurons at baseline and 20 minutes after LTP pairing (post-stimulation). Right: Normalized mean response amplitudes at 18–20 minutes of recovery; *P = 0.035, 2-tailed unpaired t test (n = 14 and 10, Mecp2-null and +ChABC Mecp2-null, respectively).