Herein we examined the effects of the Kcnj6 gene dose on behavioral and cognitive phenotypes in the Ts65Dn mouse model of DS. Genetically normalizing Kcnj6 gene dose reduced to 2N levels the Kir3.2 protein subunit of inwardly-rectifying potassium channels, restored synaptic plasticity in the DG, and improved long-term memory. Our findings are evidence that increased gene dose for Kcnj6 is necessary for deficits in hippocampal synaptic plasticity and hippocampally-mediated tests of long-term memory in a mouse model of DS.
