Upregulated SK2 Expression and Impaired CaMKII Phosphorylation Are Shared Synaptic Defects Between 16p11.2del and 129S:Δdisc1 Mutant Mice

Ion channel gating and kinase regulation of N-methyl-D-aspartate receptor 1 activity are fundamental mechanisms that govern synaptic plasticity. In this study, we showed that two mutant models (16p11.2del and Delta disc1) that recapitulate aspects of human cognitive disorders shared a similar defect in N-methyl-D-aspartate receptor 1-dependent synaptic function. Our results demonstrate that the expression of small-conductance potassium channels (SK2 or KCa2.2) was significantly upregulated in the hippocampus and prefrontal cortex of 16p11.2del and 129S:Delta disc1 mutant mice. Likewise, both mutant strains exhibited an impairment of table286-1759091418817641 phosphorylation of calcium-calmodulin-dependent kinase II (CaMKII) in the hippocampus and prefrontal cortex. In vivo neural recordings revealed that increased SK2 expression and impaired table286-1759091418817641 phosphorylation of CaMKII coincide with a prolonged interspike interval in the hippocampal cornu ammonis-1 (CA1) field for both 16p11.2del and 129S:Delta disc1 mutant mice. These findings suggest that alteration of small conductance channels and table286-1759091418817641 phosphorylation of CaMKII are likely shared factors underlying behavioral changes in these two genetic mouse models.