In contrast to the evidence that increased Kcnj6 dose contributes to deficits in synaptic plasticity and long-term memory, we found no evidence that it plays a role in working memory. Impaired working memory is characteristic of DS (Baddeley and Jarrold, 2007; Gathercole and Alloway, 2006; Jarrold and Baddeley, 2001; Lanfranchi et al., 2009) and is also abnormal in Ts65Dn and other genetic models of DS (Bimonte-Nelson et al., 2003; Dowdy-Sanders and Wenger, 2006; Kleschevnikov et al., 2012a; Whitney and Wenger, 2012). Though we failed to detect an effect of increased Kcnj6 dose on working memory as examined in the Y-maze, we did observe normalization of exploratory behavior during Y-maze testing, suggesting that Kcnj6 dose may play a role in exploration in the context of this test. We note that deficient working memory has not responded to most of the treatments restoring long-term memory in genetic models of DS (Kleschevnikov et al., 2012a; Lysenko et al., 2014). A likely explanation is that the deficiency in working memory is genetically and mechanistically distinct from the deficits in long-term memory and synaptic plasticity, as studied herein.
