Fluoxetine impacts a number of aspects of neuronal synaptic function. Best known for its effect on serotonin reuptake (Fuller and Wong, 1977), it has also been shown to inhibit potassium channels containing Kir3.2 subunits (Kobayashi et al., 2003). To assess whether pharmacological suppression of signaling through the Kir3.2 channels affects synaptic plasticity in the Ts65Dn mice, STP and LTP were examined in the Ts65Dn DG during bath application of fluoxetine (Fig. 7). Fluoxetine (10 μM) or vehicle were applied for 30 min (15 min before and 15 min after the tetanization). There was no effect on baseline responses (Fig. 7A). Synaptic plasticity was significantly impaired in vehicle-treated Ts65Dn vs. 2N slices (Fig. 7, red vs. blue). Application of fluoxetine improved both STP and LTP in Ts65Dn slices (Fig. 7, light green) to levels that were not statistically different than in 2N slices (p = 0.28 and 0.20 for STP and LTP respectively). Interestingly, fluoxetine affected neither STP (Veh: 111.1 ± 2.9%, n = 13; Flx: 113.7 ± 5.2%, n = 7; p = 0.64) nor LTP (Veh: 110.5 ± 2.4%,
