the Kir3.2 potassium channels. Fluoxetine improved both STP and LTP in the DG of Ts65Dn mice. Since fluoxetine is an inhibitor of serotonin reuptake, it raises the question of whether the finding may be due to increased serotonin levels. However, serotonin in the DG is reported to suppress LTP (Sakai and Tanaka, 1993). Thus, our findings are consistent with the effect of the drug on Kir3.2 channels. Interestingly, early treatment of neonatal (p3–p15) Ts65Dn mice with fluoxetine rescued neurogenesis and cognitive behavior (Bianchi et al., 2010). Although multiple effects may account for this change, suppression of Kir3.2 channels may contribute. Studies using selective inhibitors of Kir3.2 channels will be needed to confirm that pharmacological approaches can be used to explore and treat cognitive deficits in DS.
