The in vivo PARP1 activity regulates epileptic behavior (A-D) and graphical model summarizing the molecular mechanism of the KIF4 mutation-induced epilepsy (E). (A–D) The results of the PTZ kindling test. The chart representing the seizure stage classification (A) of the individual scores from mice with indicated genotypes and treatments, before and after the PTZ injection. Statistical analysis results of the cumulative number of maximum (B) and all (C) seizure stage, and the ratio of the occurrence of stage 4 (D). Data are presented as mean ± SEM (n = 10 mouse pairs). ****P < 0.0001 (two-way ANOVA). (E) Schematic model of the involvement of KIF4 in epileptogenesis. (a) The WT-KIF4 moderately binds to PARP1, and the cell exhibits a baseline level of PAR in the nucleus. (a′) Mut-KIF4 excessively binds to PARP1, and the cell exhibits a dramatically inhibited PARP1 activity. (b and b′) The suppressed PARP1 activity can alter the TrkB-KCC2 expression in the mutant group. Meanwhile, the aberrant protein expression triggers a higher intracellular chloride concentration. (c–d′) Subsequently, the hyper-branched dendrites and immature dendritic spines are dominantly observed in the mutant neuron.