Lack of UBE3A-Mediated Regulation of Synaptic SK2 Channels Contributes to Learning and Memory Impairment in the Female Mouse Model of Angelman Syndrome

Figure 3

Impairment of NMDA receptor-dependent hippocampal synaptic transmission and activity-dependent synaptic plasticity in hippocampal slices from female AS mice. (a) Reversal of LTP impairment in AS mice by SK2 channel blocker, apamin. Slopes of fEPSPs were normalized to the average values recorded during the 10-min baseline. (b) of fEPSPs measured 40 min after TBS in different groups. slices from 4-5 mice, , # (one-way ANOVA followed by Dunnett’s test, ). (c) LTD in hippocampal slices from AS mice is blocked by apamin. (d) of fEPSPs measured 45 min after LFS in different groups. slices from 3 mice, , ## (one-way ANOVA followed by Dunnett’s test, ). (e) and (f) Effects of apamin treatment on NMDAR-mediated synaptic responses (NfEPSPs). (e) Representative traces. (1) Mg²⁺-free aCSF containing 10 μM CNQX (control), (2) Apamin treatment, (3) D-AP5 treatment. Scale bar, 0.5 mV/10 ms. (f) Quantification of NfEPSPs. Data are expressed as % of values in WT hippocampal slices before apamin treatment (WT control). slices from 3 mice, , # (two-way ANOVA followed by the Tukey test; for genotype, , for treatment, , for interaction, ). Traces of AMPAR fEPSPs indicate that synaptic responses before initiation of NfEPSP recording are similar between AS and WT mice.

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