Figure 10.

TRIP8b^−/−, HCN2^ap/ap, and HCN1^−/− mice exhibit reduced depression-like behavior, and TRIP8b^−/− mice exhibit impaired motor learning and normal hippocampal-dependent learning and memory. A, Water maze training trials. Distance traveled to reach the hidden platform over time (n = 18 littermate pairs). B, Water maze probe trial. Percentage time spent in each quadrant of the maze (n = 18 littermate pairs; ^#p < 0.05, ^###p < 0.001 vs target quadrant, planned comparisons, contrast analysis). C, Contextual fear conditioning. Percentage time spent freezing during initial habituation period (pretrain) and during contextual memory test (context) 24 h later (n = 19 littermate pairs). D, Rotarod. Time to fall off accelerating rotating rod (n = 19 littermate pairs; *p < 0.05, ***p < 0.001 vs TRIP8b^+/+, planned comparisons, contrast analysis). E, FST on TRIP8b^−/− and HCN1^−/− mice along with respective controls. Total time immobile [*p < 0.05, TRIP8b^−/− vs TRIP8b^+/+, n = 19 littermate pairs, two-way ANOVA, main effect of genotype; ***p < 0.001, HCN1^−/− vs HCN1^+/+, n = 14 (HCN1^−/−); n = 16 (HCN1^+/+), unpaired t test]. F, TST on TRIP8b^−/−, HCN1^−/−, and HCN2^ap/ap mice along with respective controls. Total time immobile [*p < 0.05, TRIP8b^−/− vs TRIP8b^+/+, n = 19 littermate pairs, two-way ANOVA, main effect of genotype; *p < 0.05, HCN1^−/− vs HCN1^+/+, n = 15 (HCN1^−/−), n = 17 (HCN1^+/+), unpaired t test; ***p < 0.001, HCN2^ap/ap vs HCN2^+/+, n = 7 each, unpaired t test].