Fig. 4

Pharmacological inhibition of ErbB4 kinase activity eliminates the effects of KD on inhibitory synaptic activity and seizure resistance. A Representative eIPSC traces from pyramidal neurons in the CA1 region. Scale bars, 100 ms and 1000 pA. B AG1478 treatment (5 µM) diminished the effect of KD on eIPSC amplitudes. n = 18 neurons from 3 mice (CD + vehicle); n = 14 neurons from 3 mice (KD + vehicel); n = 18 neurons from 3 mice (CD + AG1478); n = 14 neurons from 3 mice (KD + AG1478). Two-way ANOVA, “CD + Vehicle” vs “KD + Vehicle”, F_(1,267) = 18.68, P < 0.0001; “CD + TSA” vs “KD + TSA”, F_(1,270) = 3.43, P = 0.0651. C Representative sIPSC traces. Scale bars, 2 s and 20 pA. D AG1478 treatment diminished the effect of KD on sIPSC frequency. n = 13 neurons from 3 mice (CD + vehicle); n = 14 neurons from 3 mice (KD + vehicle); n = 12 neurons from 3 mice (CD + AG1478); n = 14 neurons from 3 mice (KD + AG1478). One-way ANOVA, F_(3,49) = 11.25, P < 0.0001. CD + vehicle vs KD + vehicle, P = 0.007; CD + TSA vs KD + TSA, P = 0.9996. E Schematic of experimental design. After 3 weeks of diet feeding, C57 mice were injected with AG1478 (5 mM, 2 µl) into the lateral ventricle. 30 min later, KA was infused to induce seizures. F AG1478 treatment diminished the effect of KD on averaged seizure score. n = 7 per group. One-way ANOVA, F_(3,24) = 16.46, P < 0.0001. CD + vehicle vs KD + vehicle, P = 0.0041 CD + TSA vs KD + TSA, P = 0.7313. n.s. indicates not significant. * indicates p < 0.05; ** indicates p < 0.01; *** indicates p < 0.001