Segmental trisomy 16 (Ts65Dn) mice were purchased from the Jackson Laboratory, Bar Harbor, ME, stock #001924. Heterozygous Kcnj6+/− mice (129/sv–C57BL/6 hybrid crosses) were a gift from Dr. L. Jan (UCSF). These mice were characterized in a number of previous studies (Blednov et al., 2001; Mitrovic et al., 2003; Signorini et al., 1997). Ts65Dn:Kcnj6++− mice were the result of crossing female Ts65Dn with male Kcnj6+/− mice. Diploid (2N:Kcnj6++) and trisomic (Ts65Dn:Kcnj6+++) mice served as controls. To minimize the possible effect of the mixed genetic background, only littermate male mice were used in all experiments. The body weight was examined in 1–12 month old mice. All other experiments were performed using 4–6 month old mice. Ts65Dn and 2N mice were used to investigate fluoxetine effects on synaptic plasticity. The animals were housed 2 to 4 per cage with a 12 h light-dark cycle and ad lib access to food and water. Genotype of all animals was confirmed after completing experiments. For genotyping, tail samples were used to extract genomic DNA. A quantitative polymerase chain reaction protocol developed by the Jackson Laboratory, Bar