Enhancement of long-term memory suggests that reducing Kcnj6 gene dose may impact synaptic plasticity. To assess changes in hippocampal synaptic plasticity, we examined STP and LTP in the dentate gyrus (DG) (Fig. 6). Both STP and LTP were significantly reduced (p = 0.016 for STP and 0.018 for LTP) in Ts65Dn:Kcnj6+++ vs. 2N:Kcnj6++ slices (Fig. 6A, B, red vs. blue). Restoration of Kcnj6 to that in 2N mice resulted in synaptic plasticity in Ts65Dn equivalent to that observed in slices from 2N mice (Fig. 6A, green vs. blue dots). In fact, neither STP nor LTP were different in Ts65Dn:Kcnj6++− vs. 2N:Kcnj6++ mice (p = 0.29 for STP and 0.44 for LTP) (Fig. 6B, green vs. blue bars). Accordingly, both STP and LTP were greater in Ts65Dn:Kcnj6++− vs. Ts65Dn:Kcnj6+++ mice (p = 0.021 for STP and 0.047 for LTP) (Fig. 6, green vs. red). Increased Kcnj6 dose was therefore necessary for deficits in both STP and LTP in the DG of Ts65Dn mice.