Effect of intracerebroventricular injection of NRG1177-246 on E/I balance and KA-induced seizure in neuropsin-KO mice. (a) Expression of cFos (green) in ErbB4-positive neurons (red), parvalbumin (PV)-positive interneurons (blue) and pyramidal neurons at 4 h after KA administration in vehicle- (upper panel) or NRG1177-246-injected (lower panel) neuropsin-KO mice. Yellow arrows indicate ErbB4-positive neurons expressing cFos. White arrowheads indicate ErbB4-positive neurons that do not express cFos. Regions inside the boxes are enlarged in the inset images (scale bar, 20 μm). (b) Quantitative analysis of cFos expression in ErbB4-positive neurons, PV-positive interneurons, and pyramidal neurons in the vehicle- (white bars) and NRG1177-246-injected (black bars) neuropsin-KO mice shown in a. Significantly more ErbB4-positive neurons and parvalbumin-positive interneurons were immunoreactive for cFos in NRG1177-246-injected neuropsin-KO mice than in vehicle-injected mice (Mann–Whitney U test, *P=0.0286 vs vehicle); by contrast, the number of cFos-immunoreactive pyramidal neurons in NRG1177-246-injected neuropsin-KO mice was significantly lower than that in vehicle-injected mice (Mann–Whitney U test, *P=0.0286 vs vehicle). (c) E/I balance, defined as the ratio between the fractions of pyramidal neurons and parvalbumin-positive interneurons expressing cFos, in vehicle- (white bar) and NRG1177-246-injected (black bar) neuropsin-KO mice. The E/I balance in NRG1177-246-injected neuropsin-KO mice was significantly lower than that in vehicle-injected mice (Mann–Whitney U test, *P=0.0286 vs vehicle). Numbers inside the columns indicate n. (d) Time course of the seizure score in vehicle- or NRG1177-246-injected neuropsin-KO mice after KA administration. The seizure score for NRG1177-246-injected mice (black circles; n=5 mice) was significantly lower than that for vehicle-injected mice (white circles; n=5 mice) only at 4 h after KA administration (F(1,8)=1.134; *P=0.019; two-way ANOVA with the Sidak post-hoc test). The arrow denotes the point of vehicle or NRG1177-246 injection. Error bars indicate the SEM. E/I balance, excitation-inhibition balance; KA, kainate; KO, knockout; NRG1, neuregulin 1.