Collectively, these findings demonstrate that MCs’ hypo-excitability in Fmr1 KO mice results in circuit E/I imbalance that compromises the dentate information processing functions, and that circuit-based interventions, such as inhibition of Kv7, could be a potential therapeutic strategy to re-normalize the circuit E/I balance and ameliorate dentate dysfunction in FXS. This evidence concerns the gene FMR1 and fragile X syndrome.