Impairment of hippocampus-dependent long-term memory is a hallmark of DS that is recapitulated in genetic models of DS. To assess the impact of Kcnj6 dose on long-term memory, we used the novel object recognition test with a retention period of 24 h. In prior studies, this test consistently demonstrated impairment of long-term memory in Ts65Dn mice (Fernandez et al., 2007; Kleschevnikov et al., 2012a; Lysenko et al., 2014). On average, mice of all genotypes spent equal time investigating objects during both the acquisition (p = 0.16–0.39) and testing (p = 0.3–0.75; Fig. 5A). However, time for exploration of new objects tended to be lower, while time for exploration of old objects higher in Ts65Dn:Kcnj6+++ vs. 2N:Kcnj6++ mice during testing resulting in reduced discrimination index in Ts65Dn:Kcnj6+++ mice (F1,13 = 2.24; p = 0.02) (Fig. 5B). Similar reduction of discrimination index was observed in Ts65Dn:Kcnj6+++ vs. Ts65Dn:Kcnj6++− mice (F1,13 = 2.15; p = 0.025), while there was no difference between Ts65Dn:Kcnj6++− and 2N:Kcnj6++ groups (F1,35 = 0.11; p = 0.46) (Fig. 5B). One factor affecting long-term memory is anxiety. To assess
