for a number of postsynaptic metabotropic receptors (Luscher et al., 1997; Mark and Herlitze, 2000; Yamada et al., 1998). As predicted by increased dose, the Kir3.2 product of Kcnj6 is increased in Ts65Dn mice (Harashima et al., 2006; Kleschevnikov et al., 2012b; Kleschevnikov et al., 2005). Suggesting a physiologically meaningful contribution for increased Kir3.2 in these mice, there was increased signaling through postsynaptic GABAB receptors in both primary cultures of hippocampal neurons (Best et al., 2007) and acute hippocampal slices (Best et al., 2012; Kleschevnikov et al., 2012b). In addition, suppressing enhanced GABAB/Kir3.2 signaling by treating with selective GABAB receptor antagonists restored synaptic plasticity and long-term memory in Ts65Dn mice (Kleschevnikov et al., 2012a). Recently, cognitive assessment in a series of mouse genetic models bearing distinct sets of genes within DSCR pointed to a contribution of Kcnj6 (Jiang et al., 2015).
