Fig. 3
KD promotes inhibitory synaptic activity and suppresses seizures via histone acetylation. A Diagram of hippocampal slice recording. Pyramidal neurons in the CA1 region were clamped in whole-cell configuration. Evoked postsynaptic currents were recorded under stimulation by using a concentric bipolar electrode. B Representative eIPSC traces from pyramidal neurons in the CA1 region. Scale bars, 100 ms and 1000 pA. C TSA treatment (i.p., 5 mg/kg body weight) diminished the effect of KD on eIPSC amplitudes. n = 16 neurons from 4 mice (CD + vehicle); n = 21 neurons from 4 mice (KD + vehicel); n = 16 neurons from 4 mice (CD + TSA); n = 16 neurons from 4 mice (KD + TSA). Two-way ANOVA, “CD + Vehicle” vs “KD + Vehicle”, F(1,315) = 28.27, P < 0.0001; “CD + TSA” vs “KD + TSA”, F(1,270) = 0.0771, P = 0.7815. D Representative spontaneous inhibitory postsynaptic current (sIPSC) traces. Scale bars, 2 s and 20 pA. E TSA treatment diminished the effect of KD on sIPSC frequency. n = 17 neurons from 4 mice (CD + vehicle); n = 13 neurons from 4 mice (KD + vehicle); n = 13 neurons from 4 mice (CD + TSA); n = 13 neurons from 4 mice (KD + TSA). One-way ANOVA, F(3,52) = 5.242, P = 0.0031. CD + vehicle vs KD + vehicle, P = 0.0044; CD + TSA vs KD + TSA, P = 0.9099. F TSA treatment exhibited little effect on sIPSC amplitude. n = 17 neurons from 4 mice (CD + vehicle); n = 13 neurons from 4 mice (KD + vehicle); n = 13 neurons from 4 mice (CD + TSA); n = 13 neurons from 4 mice (KD + TSA). One-way ANOVA, F(3,52) = 2.211, P = 0.0978. G Schematic of experimental design. After 3 weeks of diet feeding, C57 mice were injected with TSA one day before KA infusion to induce seizures. H TSA treatment diminished the effect of KD on averaged seizure score. n = 7 mice for CD + Vehicle group; n = 8 mice for KD + Vehicle group; n = 8 mice for CD + TSA group, n = 8 mice for KD + TSA group. One-way ANOVA, F(3,27) = 12.35, P < 0.0001. CD + vehicle vs KD + vehicle, P = 0.0076; CD + TSA vs KD + TSA, P = 0.9756. n.s. indicates not significant. * indicates p < 0.05; ** indicates p < 0.01; *** indicates p < 0.001