Figure 4, behavior characterization |
|
|
Social approach |
|
|
Two-way ANOVA |
|
|
ANOVA table |
p value |
F
(DFn,DFd)
|
Interaction |
p = 0.1321 |
F(3,90) = 1.920 |
Preference |
p < 0.0001 |
F(1,90) = 62.64 |
Genotype |
p = 0.1111 |
F(3,90) = 2.060 |
Bonferroni's multiple comparisons test |
Adjusted p value |
|
Novel animal, novel object |
|
|
Control VEH n = 15 |
p < 0.0001 |
|
Mutant VEH n = 10 |
p = 0.4167 |
|
Control RAPA n = 13 |
p = 0.0001 |
|
Mutant RAPA n = 14 |
p < 0.0001 |
|
Social novelty |
|
|
Two-way ANOVA |
|
|
ANOVA table |
p value |
F
(DFn,DFd)
|
Interaction |
p = 0.2467 |
F(3,96) = 1.403 |
Preference |
p < 0.0001 |
F(1,96) = 27.22 |
Genotype |
p = 0.5971 |
F(3,96) = 0.6305 |
Bonferroni's multiple comparisons test |
Adjusted p value |
|
Novel animal, novel object |
|
|
Control VEH n = 17 |
p = 0.0497 |
|
Mutant VEH n = 12 |
p > 0.9959 |
|
Control RAPA n = 17 |
p = 0.0002 |
|
Mutant RAPA n = 14 |
p = 0.0380 |
|
Social olfaction |
|
|
Two-way ANOVA |
|
|
ANOVA table |
p value |
F
(DFn,DFd)
|
Interaction |
p < 0.0001 |
F(42,1050) = 4.653 |
Scent |
p < 0.0001 |
F(14,1050) = 191.2 |
Group |
p < 0.0001 |
F(3,1050) = 46.70 |
Bonferroni's multiple comparisons test |
Adjusted p value |
|
Water |
|
|
Control VEH n = 16 vs mutant VEH n = 16 |
p > 0.9999 |
|
Control RAPA n = 21 vs mutant RAPA n = 21 |
p > 0.9999 |
|
Control VEH n = 16 vs control RAPA n = 21 |
p > 0.9999 |
|
Mutant VEH n = 16 vs mutant RAPA n = 21 |
p > 0.9999 |
|
Almond |
|
|
Control VEH n = 16 vs mutant VEH n = 16 |
p = 0.4580 |
|
Control RAPA n = 21 vs mutant RAPA n = 21 |
p > 0.9999 |
|
Control VEH n = 16 vs control RAPA n = 21 |
p > 0.9999 |
|
Mutant VEH n = 16 vs mutant RAPA n = 21 |
p = 0.6805 |
|
Social scent |
|
|
Control VEH n = 16 vs mutant VEH n = 16 |
p < 0.0001 |
|
Control RAPA n = 21 vs mutant RAPA n = 21 |
p < 0.0001 |
|
Control VEH n = 16 vs control RAPA n = 21 |
p > 0.9999 |
|
Mutant VEH n = 16 vs mutant RAPA n = 21 |
p = 0.0003 |
|
Water Y maze |
|
|
Two-way ANOVA |
|
|
ANOVA table |
p value |
F
(DFn,DFd)
|
Interaction |
p < 0.0001 |
F(15,474) = 4.925 |
Day |
p < 0.0001 |
F(15,474) = 120.6 |
Group |
p < 0.0001 |
F(15,474) = 16.75 |
Bonferroni's multiple comparisons test |
Adjusted p value |
|
Trial 1 |
|
|
Control VEH n = 15 vs mutant VEH n = 17 |
p > 0.9999 |
|
Control RAPA n = 26 vs mutant RAPA n = 25 |
p > 0.9999 |
|
Control VEH n = 15 vs control RAPA n = 26 |
p > 0.9999 |
|
Mutant VEH n = 17 vs mutant RAPA n = 25 |
p > 0.9999 |
|
Trial 2 |
|
|
Control VEH n = 15 vs mutant VEH n = 17 |
p > 0.9999 |
|
Control RAPA n = 26 vs mutant RAPA n = 25 |
p > 0.9999 |
|
Control VEH n = 15 vs control RAPA n = 26 |
p > 0.9999 |
|
Mutant VEH n = 17 vs mutant RAPA n = 25 |
p > 0.9999 |
|
Trial 3 |
|
|
Control VEH n = 15 vs mutant VEH n = 17 |
p > 0.9999 |
|
Control RAPA n = 26 vs mutant RAPA n = 25 |
p > 0.9999 |
|
Control VEH n = 15 vs control RAPA n = 26 |
p > 0.9999 |
|
Mutant VEH n = 17 vs mutant RAPA n = 25 |
p > 0.9999 |
|
Rev. trial 1 |
|
|
Control VEH n = 15 vs mutant VEH n = 17 |
p < 0.0001 |
|
Control RAPA n = 26 vs mutant RAPA n = 25 |
p = 0.0041 |
|
Control VEH n = 15 vs control RAPA n = 26 |
p = 0.3740 |
|
Mutant VEH n = 17 vs mutant RAPA n = 25 |
p > 0.9999 |
|
Rev. trial 2 |
|
|
Control VEH n = 15 vs mutant VEH n = 17 |
p < 0.0001 |
|
Control RAPA n = 26 vs mutant RAPA n = 25 |
p = 0.2559 |
|
Control VEH n = 15 vs control RAPA n = 26 |
p > 0.9999 |
|
Mutant VEH n = 17 vs mutant RAPA n = 25 |
p = 0.0006 |
|
Rev. trial 3 |
|
|
Control VEH n = 15 vs mutant VEH n = 17 |
p < 0.0001 |
|
Control RAPA n = 26 vs mutant RAPA n = 25 |
p > 0.9999 |
|
Control VEH n = 15 vs control RAPA n = 26 |
p > 0.9999 |
|
Mutant VEH n = 17 vs mutant RAPA n = 25 |
p < 0.0001 |
|
Rotarod |
|
|
Two-way ANOVA |
|
|
ANOVA table |
p value |
F
(DFn,DFd)
|
Interaction |
p = 0.9952 |
F(12,235) = 0.2504 |
Day |
p < 0.0001 |
F(4,235) = 12.38 |
Group |
p < 0.0001 |
F(3,235) = 14.26 |
Bonferroni's multiple comparisons test |
Adjusted p value |
|
Day 1 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p = 0.6610 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p = 0.2247 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Day 2 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p = 0.0119 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p = 0.0254 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Day 3 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p = 0.0294 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p = 0.0626 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Day 4 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p = 0.0748 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p = 0.1765 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Day 5 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p = 0.0073 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p = 0.3565 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p = 0.1602 |
|
Open field |
|
|
Two-way ANOVA |
|
|
Distance moved |
|
|
ANOVA table |
p value |
F
(DFn,DFd)
|
Interaction |
p = 0.9845 |
F(42,705) = 0.5823 |
Minute |
p = 0.5856 |
F(14,705) = 0.8758 |
Group |
p < 0.0001 |
F(3,705) = 9.465 |
Bonferroni's multiple comparisons test |
Adjusted p value |
|
0:00–1:00 (60 seconds) |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p > 0.9999 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p = 0.7247 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p > 0.9999 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p > 0.9999 |
|
1:00–2:00 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p > 0.9999 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p = 0.3628 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p > 0.9999 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p = 0.2082 |
|
2:00–3:00 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p > 0.9999 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p = 0.4648 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p > 0.9999 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p > 0.9999 |
|
3:00–4:00 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p > 0.9999 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p > 0.9999 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p > 0.9999 |
|
4:00–5:00 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p > 0.9999 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p = 0.2421 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p = 0.5267 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p > 0.9999 |
|
5:00–6:00 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p > 0.9999 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p > 0.9999 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p > 0.9999 |
|
6:00-7:00 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p > 0.9999 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p > 0.9999 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p > 0.9999 |
|
7:00–8:00 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p > 0.9999 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p > 0.9999 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p > 0.9999 |
|
8:00–9:00 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p > 0.9999 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p = 0.2996 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p = 0.2294 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p > 0.9999 |
|
9:00–10:00 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p > 0.9999 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p = 0.7791 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p = 0.0953 |
|
10:00–11:00 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p > 0.9999 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p > 0.9999 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p > 0.9999 |
|
11:00–12:00 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p > 0.9999 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p > 0.9999 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p > 0.9999 |
|
12:00–13:00 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p > 0.9999 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p > 0.9999 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p > 0.9999 |
|
13:00–14:00 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p > 0.9999 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p = 0.8308 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p = 0.0227 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p > 0.9999 |
|
14:00–15:00 |
|
|
Control VEH n = 12 vs mutant VEH n = 10 |
p > 0.9999 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p = 0.5178 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Time in center |
|
|
ANOVA table |
p value |
F
(DFn,DFd)
|
Interaction |
p = 0.7432 |
F(1,47) = 0.1086 |
Treatment |
p = 0.1829 |
F(1,47) = 1.827 |
Genotype |
p = 0.4546 |
F(1,47) = 0.5684 |
Bonferroni's multiple comparisons test |
Adjusted p value |
|
Control VEH n = 12 vs mutant VEH n = 10 |
p > 0.9999 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p = 0.8279 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p = 0.9436 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p = 0.4841 |
|
Elevated plus maze |
|
|
Two-way ANOVA |
|
|
Open arms |
|
|
ANOVA table |
p value |
F
(DFn,DFd)
|
Interaction |
p = 0.1322 |
F(1,47) = 2.347 |
Treatment |
p = 0.6031 |
F(1,47) = 0.2741 |
Genotype |
p = 0.4877 |
F(1,47) = 0.4892 |
Bonferroni's multiple comparisons test |
Adjusted p value |
|
Control VEH n = 12 vs mutant VEH n = 10 |
p = 0.2909 |
|
Control RAPA n = 13 vs mutant RAPA n = 16 |
p > 0.9999 |
|
Control VEH n = 12 vs control RAPA n = 13 |
p = 0.3207 |
|
Mutant VEH n = 10 vs mutant RAPA n = 16 |
p = 0.9617 |
|
Figure 5, cell survival |
|
|
Cell count |
|
|
Two-way ANOVA |
|
|
ANOVA table |
p value |
F
(DFn,DFd)
|
Interaction |
p = 0.0006 |
F(1,10) = 24.22 |
Treatment |
p = 0.0015 |
F(1,10) = 18.56 |
Genotype |
p < 0.0001 |
F(1,10) = 41.95 |
Bonferroni's multiple comparisons test |
Adjusted p value |
|
Control VEH n = 4 vs mutant VEH n = 3 |
p < 0.0001 |
|
Control RAPA n = 4 vs mutant RAPA n = 3 |
p = 0.5947 |
|
Control VEH n = 4 vs control RAPA n = 4 |
p > 0.9999 |
|
Mutant VEH n = 3 vs mutant RAPA n = 3 |
p = 0.0002 |
|
Mutant VEH n = 3 vs control RAPA n = 3 |
p = 0.0001 |
|
Figure 6, physiology |
|
|
PC intrinsic firing rate |
|
|
Two-way ANOVA |
|
|
ANOVA table |
p value |
F
(DFn,DFd)
|
Interaction |
p = 0.0100 |
F(1,113) = 6.870 |
Treatment |
p = 0.0173 |
F(1,113) = 5.832 |
Genotype |
p = 0.0110 |
F(1,113) = 6.681 |
Bonferroni's multiple comparisons test |
Adjusted p value |
|
Control VEH n = 43 vs mutant VEH n = 16 |
p = 0.0008 |
|
Control RAPA n = 41 vs mutant RAPA n = 17 |
p > 0.9999 |
|
Control VEH n = 43 vs control RAPA n = 41 |
p > 0.9999 |
|
Mutant VEH n = 16 vs mutant RAPA n = 17 |
p = 0.0072 |
|
Mutant VEH n = 16 vs control RAPA n = 41 |
p = 0.0042 |
|
PC evoked responses |
|
|
Two-way ANOVA |
|
|
ANOVA table |
p value |
F
(DFn,DFd)
|
Interaction |
p = 0.2388 |
F(42,1344) = 1.149 |
Current step |
p < 0.0001 |
F(14,1344) = 564.4 |
Group |
p < 0.0001 |
F(3,1344) = 99.38 |
Bonferroni's multiple comparisons test |
Adjusted p value |
|
Control VEH n = 39 vs mutant VEH n = 17 |
p < 0.0001 |
|
Control RAPA n = 26 vs mutant RAPA n = 17 |
p > 0.9999 |
|
Control VEH n = 39 vs control RAPA n = 26 |
p = 0.0326 |
|
Mutant VEH n = 17 vs mutant RAPA n = 17 |
p = 0.0070 |
|
Mutant VEH n = 17 vs control RAPA n = 26 |
p < 0.0001 |
|
Membrane input resistance |
|
|
Two-way ANOVA |
|
|
ANOVA table |
p value |
F
(DFn,DFd)
|
Interaction |
p = 0.4496 |
F(1,71) = 0.5780 |
Treatment |
p = 0.9045 |
F(1,71) = 0.01451 |
Genotype |
p = 0.0316 |
F(1,71) = 4.808 |
Bonferroni's multiple comparisons test |
Adjusted p value |
|
Control VEH n = 16 vs mutant VEH n = 15 |
p = 0.1140 |
|
Control RAPA n = 25 vs mutant RAPA n = 19 |
p = 0.5429 |
|
Control VEH n = 16 vs control RAPA n = 25 |
p > 0.9999 |
|
Mutant VEH n = 15 vs mutant RAPA n = 19 |
p > 0.9999 |
|
Mutant VEH n = 15 vs control RAPA n = 25 |
p = 0.5985 |
|
Membrane capacitance |
|
|
Two-way ANOVA |
|
|
ANOVA table |
p value |
F
(DFn,DFd)
|
Interaction |
p = 0.4741 |
F(1,62) = 0.5186 |
Treatment |
p = 0.2037 |
F(1,62) = 1.650 |
Genotype |
p = 0.1059 |
F(1,62) = 2.692 |
Membrane time constant |
|
|
Two-way ANOVA |
|
|
ANOVA table |
p value |
F
(DFn,DFd)
|
Interaction |
p = 0.2520 |
F(1,62) = 1.337 |
Treatment |
p = 0.2431 |
F(1,62) = 1.389 |
Genotype |
p = 0.2269 |
F(1,62) = 1.490 |
Mouse age at time of testing (all experiments) |
|
|
|
4-week treatment paradigm |
|
Rotarod |
9 weeks |
Rotarod |
Open field |
10 weeks |
Open field |
Elevated plus maze |
10 weeks |
Elevated plus maze |
Social interaction (three-chamber) |
11 weeks |
Social interaction (three-chamber) |
Social olfaction |
11 weeks |
Social olfaction |
Water Y maze |
12 weeks |
Water Y maze |
Immunohistochemistry |
9–12 weeks |
Immunohistochemistry |
Acute slice physiology |
9–12 weeks |
Acute slice physiology |