Figure 6. GIRK-dependent signaling and NOR performance in APP/PS1 mice.
(A) Representative baclofen-induced outward currents (200 μM; Vhold= −60 mV) and their reversal by CGP54626 (2 μM) in dHPC CA1 pyramidal neurons from 6-month-old male and female APP/PS1 and wild-type control littermates. Scale bars: 100 pA/50 s. (B) Ibaclofen summary in dHPC CA1 pyramidal neurons from 6-month-old and 12-month-old APP/PS1 (+) and wild-type control (−) littermates. Male data were collected from 10 neurons from 3 mice (6m/−), 8 neurons from 3 mice (6m/+), 8 neurons from 2 mice (12m/−), 8 neurons from 2 mice (12m/+); female data were collected from 9 neurons from 3 mice (6m/−), 9 neurons from 2 mice (6m/+), 6 neurons from 2 mice (12m/−), 8 neurons from 2 mice (12m/+). Data were analyzed by two-way ANOVA and Šídák’s multiple comparisons: *P<0.05,***P<0.001. (C) Recognition index in the NOR test for 6-month-old male (8 mice per group) and female (8 mice per group) APP/PS1 (+) and wild-type control (−) littermates. P>0.05, unpaired t test. (D) Representative section from a 12-month-old male APP/PS1 mouse, 3 weeks after bilateral intra-HPC infusion of AAV8-CaMKIIα-GIRK2. Scale bar: 1 mm. (E) Recognition index in the NOR test for 12-month-old male APP/PS1 (+) and wild-type control (−) littermates, measured 2–3 weeks after bilateral intra-HPC infusion of GFP or GIRK2 (G2) expression vectors. Group sizes were 7 (GFP/−), 7 (GFP/+), 7 (G2/−), and 6 (G2/+) male mice and 7 (GFP/−), 7 (GFP/+), 7 (G2/−), and 6 (G2/+) female mice. Data were analyzed by two-way ANOVA and Šídák’s multiple comparisons: *P<0.05,**P<0.01 within genotype; #P<0.05,##P<0.01 within viral treatment. Data in (B, C, E) are presented as mean ± SEM.