Fig. 2
Deleting or disrupting HDAC3 ameliorates age-related impairments in synaptic plasticity. a Mean ± SEM fEPSP slope recordings in hippocampal slices from young (3-m.o.) HDAC3flox/flox mice or HDAC3+/+ littermates 2-weeks after hippocampal AAV-Cre infusion. Deleting HDAC3 enhanced theta burst-induced LTP in the young hippocampus. Scale bar: 1 mV per 5 ms. b The same stimulation caused a gradual decay toward baseline in slices from old (18-m.o.) HDAC3+/+ mice. Deleting HDAC3 (HDAC3flox/flox) restored a greater level of stable potentiation relative to HDAC3+/+ littermates. Scale bar: 1 mV per 5 ms. c Summary graph showing mean fEPSP slope 60 m after stimulation. Potentiation was significantly enhanced by HDAC3 deletion in slices from both young and old mice. Deleting HDAC3 in the 18-m.o. hippocampus produced LTP comparable to that of 3-m.o. wildtype mice (Two-way ANOVA: main effects of Age (F(1,33) = 80.8, p < 0.0001) and Genotype (F(1,33) = 75.5, p < 0.0001), Sidak’s post hoc tests, ***p < 0.0001, n = 8, 7, 8, 14 slices from 3, 3, 3, 6 mice; all male). d Mean ± SEM fEPSP slope recordings in hippocampal slices from young (3-m.o.) mice two weeks after hippocampal AAV-HDAC3(Y298H) or AAV-EV infusion. Disrupting HDAC3 activity enhanced LTP in the young hippocampus. Scale bar: 1 mV per 5 ms. e The same stimulation protocol failed to produce stable potentiation in slices from 18-m.o. mice, but this impairment was overcome by disrupting HDAC3 activity (AAV-HDAC3(Y298H)). Scale bar: 1 mV per 5 ms. f Summary graph. Potentiation was significantly enhanced by HDAC3 disruption in slices from both young and old mice. Disrupting HDAC3 activity in the 18-m.o. hippocampus with AAV-HDAC3(Y298H) produced LTP comparable to that of 3-m.o. wildtype mice (Two-way ANOVA: main effects of Age (F(1,19) = 62.8, p < 0.0001) and Genotype (F(1,19) = 63.4, p < 0.0001), Sidak’s post hoc tests, ***p < 0.0001, n = 6, 6, 6, 5 slices from 4, 4, 4, 4 mice; all male). g Input/output (I/O) curves and h paired-pulse facilitation (PPF) were comparable between HDAC3+/+ and HDAC3flox/flox slices. i I/O curves and j PPF were similar between AAV-EV and AAV-HDAC3(Y298H) slices. Data are presented as mean ± SEM
