Table 1.
Statistics for P7–P63 cohort
| Test/experiment | ||
|---|---|---|
| Figure 1, behavior characterization | ||
| Social approach | ||
| Two-way ANOVA | ||
| ANOVA table | p value | F (DFn,DFd) |
| Interaction | p = 0.0001 | F(3,118) = 7.344 |
| Preference | p < 0.0001 | F(1,118) = 52.56 |
| Genotype | p = 0.2661 | F(3,118) = 1.336 |
| Bonferroni's multiple comparisons test | Adjusted p value | |
| Novel animal, novel object | ||
| Control VEH n = 18 | p = 0.0022 | |
| Mutant VEH n = 14 | p > 0.9999 | |
| Control RAPA n = 17 | p < 0.0001 | |
| Mutant RAPA n = 14 | p < 0.0001 | |
| Social novelty | ||
| Two-way ANOVA | ||
| ANOVA table | p value | F (DFn,DFd) |
| Interaction | p = 0.2465 | F(3,112) = 1.400 |
| Preference | p < 0.0001 | F(1,112) = 23.17 |
| Genotype | p = 0.1095 | F(3,112) = 2.060 |
| Bonferroni's multiple comparisons test | Adjusted p value | |
| Novel animal, novel object | ||
| Control VEH n = 17 | p = 0.0199 | |
| Mutant VEH n = 12 | p > 0.9999 | |
| Control RAPA n = 17 | p = 0.0059 | |
| Mutant RAPA n = 14 | p = 0.0051 | |
| Social olfaction | ||
| Two-way ANOVA | ||
| ANOVA table | p value | F (DFn,DFd) |
| Interaction | p < 0.0001 | F(42,735) = 2.641 |
| Scent | p < 0.0001 | F(14,735) = 39.46 |
| Group | p < 0.0001 | F(3,735) = 37.52 |
| Bonferroni's multiple comparisons test | Adjusted p value | |
| Water | ||
| Control VEH n = 19 vs mutant VEH n = 12 | p = 0.8170 | |
| Control RAPA n = 12 vs mutant RAPA n = 10 | p > 0.9999 | |
| Control VEH n = 19 vs control RAPA n = 12 | p > 0.9999 | |
| Mutant VEH n = 12 vs mutant RAPA n = 10 | p > 0.9999 | |
| Almond | ||
| Control VEH n = 19 vs mutant VEH n = 12 | p > 0.9999 | |
| Control RAPA n = 12 vs mutant RAPA n = 10 | p > 0.9999 | |
| Control VEH n = 19 vs control RAPA n = 12 | p = 0.3913 | |
| Mutant VEH n = 12 vs mutant RAPA n = 10 | p = 0.1125 | |
| Social scent | ||
| Control VEH n = 19 vs mutant VEH n = 12 | p = 0.0149 | |
| Control RAPA n = 12 vs mutant RAPA n = 10 | p > 0.9999 | |
| Control VEH n = 19 vs control RAPA n = 12 | p = 0.0010 | |
| Mutant VEH n = 12 vs mutant RAPA n = 10 | p < 0.0001 | |
| Grooming | ||
| Two-way ANOVA | ||
| ANOVA table | p value | F (DFn,DFd) |
| Interaction | p = 0.7009 | F(1,55) = 0.1491 |
| Treatment | p = 0.6617 | F(1,55) = 0.1935 |
| Group | p < 0.0001 | F(1,55) = 19.07 |
| Bonferroni's multiple comparisons test | Adjusted p value | |
| Control VEH n = 10 vs mutant VEH n = 14 | p = 0.0067 | |
| Control RAPA n = 18 vs mutant RAPA n = 17 | p = 0.0053 | |
| Control VEH n = 10 vs control RAPA n = 18 | p > 0.9999 | |
| Mutant VEH n = 14 vs mutant RAPA n = 17 | p > 0.9999 | |
| Water Y maze | ||
| Two-way ANOVA | ||
| ANOVA table | p value | F (DFn,DFd) |
| Interaction | p < 0.0001 | F(15,378) = 3.671 |
| Day | p < 0.0001 | F(5,378) = 83.08 |
| Group | p < 0.0001 | F(3,378) = 12.10 |
| Bonferroni's multiple comparisons test | Adjusted p value | |
| Trial 1 | ||
| Control VEH n = 20 vs mutant VEH n = 17 | p > 0.9999 | |
| Control RAPA n = 17 vs mutant RAPA n = 13 | p > 0.9999 | |
| Control VEH n = 20 vs control RAPA n = 17 | p > 0.9999 | |
| Mutant VEH n = 17 vs mutant RAPA n = 13 | p > 0.9999 | |
| Trial 2 | ||
| Control VEH n = 20 vs mutant VEH n = 17 | p > 0.9999 | |
| Control RAPA n = 17 vs mutant RAPA n = 13 | p > 0.9999 | |
| Control VEH n = 20 vs control RAPA n = 17 | p > 0.9999 | |
| Mutant VEH n = 17 vs mutant RAPA n = 13 | p > 0.9999 | |
| Trial 3 | ||
| Control VEH n = 20 vs mutant VEH n = 17 | p > 0.9999 | |
| Control RAPA n = 17 vs mutant RAPA n = 13 | p > 0.9999 | |
| Control VEH n = 20 vs control RAPA n = 17 | p > 0.9999 | |
| Mutant VEH n = 17 vs mutant RAPA n = 13 | p > 0.9999 | |
| Rev. trial 1 | ||
| Control VEH n = 20 vs mutant VEH n = 17 | p < 0.0001 | |
| Control RAPA n = 17 vs mutant RAPA n = 13 | p < 0.0001 | |
| Control VEH n = 20 vs control RAPA n = 17 | p > 0.9999 | |
| Mutant VEH n = 17 vs mutant RAPA n = 13 | p > 0.9999 | |
| Rev. trial 2 | ||
| Control VEH n = 20 vs mutant VEH n = 17 | p = 0.0186 | |
| Control RAPA n = 17 vs mutant RAPA n = 13 | p = 0.0846 | |
| Control VEH n = 20 vs control RAPA n = 17 | p > 0.9999 | |
| Mutant VEH n = 17 vs mutant RAPA n = 13 | p > 0.9999 | |
| Rev. trial 3 | ||
| Control VEH n = 20 vs mutant VEH n = 17 | p > 0.9999 | |
| Control RAPA n = 17 vs mutant RAPA n = 13 | p > 0.9999 | |
| Control VEH n = 20 vs control RAPA n = 17 | p > 0.9999 | |
| Mutant VEH n = 17 vs mutant RAPA n = 13 | p > 0.9999 | |
| Rotarod | ||
| Two-way ANOVA | ||
| ANOVA table | p value | F (DFn,DFd) |
| Interaction | p < 0.0001 | F(12,390) = 3.767 |
| Day | p < 0.0001 | F(4,390) = 16.40 |
| Group | p < 0.0001 | F(3,390) = 70.61 |
| Bonferroni's multiple comparisons test | Adjusted p value | |
| Day 1 | ||
| Control VEH n = 25 vs mutant VEH n = 15 | p = 0.1112 | |
| Control RAPA n = 19 vs mutant RAPA n = 23 | p = 0.9056 | |
| Control VEH n = 25 vs control RAPA n = 19 | p > 0.9999 | |
| Mutant VEH n = 15 vs mutant RAPA n = 23 | p = 0.0071 | |
| Day 2 | ||
| Control VEH n = 25 vs mutant VEH n = 15 | p = 0.0001 | |
| Control RAPA n = 19 vs mutant RAPA n = 23 | p = 0.4920 | |
| Control VEH n = 25 vs control RAPA n = 19 | p > 0.9999 | |
| Mutant VEH n = 15 vs mutant RAPA n = 23 | p < 0.0001 | |
| Day 3 | ||
| Control VEH n = 25 vs mutant VEH n = 15 | p < 0.0001 | |
| Control RAPA n = 19 vs mutant RAPA n = 23 | p > 0.9999 | |
| Control VEH n = 25 vs control RAPA n = 19 | p = 0.1609 | |
| Mutant VEH n = 15 vs mutant RAPA n = 23 | p < 0.0001 | |
| Day 4 | ||
| Control VEH n = 25 vs mutant VEH n = 15 | p < 0.0001 | |
| Control RAPA n = 19 vs mutant RAPA n = 23 | p > 0.9999 | |
| Control VEH n = 25 vs control RAPA n = 19 | p = 0.0024 | |
| Mutant VEH n = 15 vs mutant RAPA n = 23 | p < 0.0001 | |
| Day 5 | ||
| Control VEH n = 25 vs mutant VEH n = 15 | p < 0.0001 | |
| Control RAPA n = 19 vs mutant RAPA n = 23 | p > 0.9999 | |
| Control VEH n = 25 vs control RAPA n = 19 | p < 0.0001 | |
| Mutant VEH n = 15 vs mutant RAPA n = 23 | p < 0.0001 | |
| Open field | ||
| Two-way ANOVA | ||
| Distance moved | ||
| ANOVA table | p value | F (DFn,DFd) |
| Interaction | p = 0.9653 | F(42,989) = 0.6378 |
| Minute | p = 0.0038 | F(14,989) = 2.318 |
| Group | p < 0.0001 | F(3,989) = 10.53 |
| Bonferroni's multiple comparisons test | Adjusted p value | |
| 0:00–1:00 (60 seconds) | ||
| Control VEH n = 20 vs mutant VEH n = 14 | p = 0.6273 | |
| Control RAPA n = 18 vs mutant RAPA n = 18 | p > 0.9999 | |
| Control VEH n = 20 vs control RAPA n = 18 | p > 0.9999 | |
| Mutant VEH n = 14 vs mutant RAPA n = 18 | p > 0.9999 | |
| 1:00–2:00 | ||
| Control VEH n = 20 vs mutant VEH n = 14 | p > 0.9999 | |
| Control RAPA n = 18 vs mutant RAPA n = 18 | p > 0.9999 | |
| Control VEH n = 20 vs control RAPA n = 18 | p > 0.9999 | |
| Mutant VEH n = 14 vs mutant RAPA n = 18 | p = 0.2082 | |
| 2:00–3:00 | ||
| Control VEH n = 20 vs mutant VEH n = 14 | p > 0.9999 | |
| Control RAPA n = 18 vs mutant RAPA n = 18 | p > 0.9999 | |
| Control VEH n = 20 vs control RAPA n = 18 | p > 0.9999 | |
| Mutant VEH n = 14 vs mutant RAPA n = 18 | p > 0.9999 | |
| 3:00–4:00 | ||
| Control VEH n = 20 vs mutant VEH n = 14 | p > 0.9999 | |
| Control RAPA n = 18 vs mutant RAPA n = 18 | p > 0.9999 | |
| Control VEH n = 20 vs control RAPA n = 18 | p > 0.9999 | |
| Mutant VEH n = 14 vs mutant RAPA n = 18 | p > 0.9999 | |
| 4:00–5:00 | ||
| Control VEH n = 20 vs mutant VEH n = 14 | p > 0.9999 | |
| Control RAPA n = 18 vs mutant RAPA n = 18 | p > 0.9999 | |
| Control VEH n = 20 vs control RAPA n = 18 | p > 0.9999 | |
| Mutant VEH n = 14 vs mutant RAPA n = 18 | p > 0.9999 | |
| 5:00–6:00 | ||
| Control VEH n = 20 vs mutant VEH n = 14 | p > 0.9999 | |
| Control RAPA n = 18 vs mutant RAPA n = 18 | p > 0.9999 | |
| Control VEH n = 20 vs control RAPA n = 18 | p = 0.0411 | |
| Mutant VEH n = 14 vs mutant RAPA n = 18 | p = 0.8482 | |
| 6:00–7:00 | ||
| Control VEH n = 20 vs mutant VEH n = 14 | p > 0.9999 | |
| Control RAPA n = 18 vs mutant RAPA n = 18 | p > 0.9999 | |
| Control VEH n = 20 vs control RAPA n = 18 | p > 0.9999 | |
| Mutant VEH n = 14 vs mutant RAPA n = 18 | p > 0.9999 | |
| 7:00–8:00 | ||
| Control VEH n = 20 vs mutant VEH n = 14 | p > 0.9999 | |
| Control RAPA n = 18 vs mutant RAPA n = 18 | p > 0.9999 | |
| Control VEH n = 20 vs control RAPA n = 18 | p = 0.4288 | |
| Mutant VEH n = 14 vs mutant RAPA n = 18 | p > 0.9999 | |
| 8:00–9:00 | ||
| Control VEH n = 20 vs mutant VEH n = 14 | p > 0.9999 | |
| Control RAPA n = 18 vs mutant RAPA n = 18 | p > 0.9999 | |
| Control VEH n = 20 vs control RAPA n = 18 | p > 0.9999 | |
| Mutant VEH n = 14 vs mutant RAPA n = 18 | p > 0.9999 | |
| 9:00–10:00 | ||
| Control VEH n = 20 vs mutant VEH n = 14 | p > 0.9999 | |
| Control RAPA n = 18 vs mutant RAPA n = 18 | p = 0.4031 | |
| Control VEH n = 20 vs control RAPA n = 18 | p > 0.9999 | |
| Mutant VEH n = 14 vs mutant RAPA n = 18 | p = 0.0953 | |
| 10:00–11:00 | ||
| Control VEH n = 20 vs mutant VEH n = 14 | p > 0.9999 | |
| Control RAPA n = 18 vs mutant RAPA n = 18 | p > 0.9999 | |
| Control VEH n = 20 vs control RAPA n = 18 | p > 0.9999 | |
| Mutant VEH n = 14 vs mutant RAPA n = 18 | p > 0.9999 | |
| 11:00–12:00 | ||
| Control VEH n = 20 vs mutant VEH n = 14 | p > 0.9999 | |
| Control RAPA n = 18 vs mutant RAPA n = 18 | p > 0.9999 | |
| Control VEH n = 20 vs control RAPA n = 18 | p > 0.9999 | |
| Mutant VEH n = 14 vs mutant RAPA n = 18 | p > 0.9999 | |
| 12:00–13:00 | ||
| Control VEH n = 20 vs mutant VEH n = 14 | p > 0.9999 | |
| Control RAPA n = 18 vs mutant RAPA n = 18 | p > 0.9999 | |
| Control VEH n = 20 vs control RAPA n = 18 | p > 0.9999 | |
| Mutant VEH n = 14 vs mutant RAPA n = 18 | p > 0.9999 | |
| 13:00–14:00 | ||
| Control VEH n = 20 vs mutant VEH n = 14 | p > 0.9999 | |
| Control RAPA n = 18 vs mutant RAPA n = 18 | p > 0.9999 | |
| Control VEH n = 20 vs control RAPA n = 18 | p = 0.4511 | |
| Mutant VEH n = 14 vs mutant RAPA n = 18 | p = 0.7478 | |
| 14:00–15:00 | ||
| Control VEH n = 20 vs mutant VEH n = 14 | p > 0.9999 | |
| Control RAPA n = 18 vs mutant RAPA n = 18 | p > 0.9999 | |
| Control VEH n = 20 vs control RAPA n = 18 | p = 0.1904 | |
| Mutant VEH n = 14 vs mutant RAPA n = 18 | p > 0.9999 | |
| Time in left | ||
| ANOVA table | p value | F (DFn,DFd) |
| Interaction | p = 0.9524 | F(1,71) = 0.003591 |
| Treatment | p = 0.3550 | F(1,71) = 0.8669 |
| Genotype | p = 0.0429 | F(1,71) = 4.250 |
| Bonferroni's multiple comparisons test | Adjusted p value | |
| Control VEH n = 20 vs mutant VEH n = 14 | p = 0.3036 | |
| Control RAPA n = 18 vs mutant RAPA n = 18 | p = 0.2924 | |
| Control VEH n = 20 vs control RAPA n = 18 | p = 0.9581 | |
| Mutant VEH n = 14 vs mutant RAPA n = 18 | p > 0.9999 | |
| Elevated plus maze | ||
| Two-way ANOVA | ||
| Open arms | ||
| ANOVA table | p value | F (DFn,DFd) |
| Interaction | p = 0.8544 | F(1,58) = 0.03400 |
| Treatment | p = 0.5133 | F(1,58) = 0.4326 |
| Genotype | p = 0.0375 | F(1,58) = 4.535 |
| Bonferroni's multiple comparisons test | Adjusted p value | |
| Control VEH n = 13 vs mutant VEH n = 11 | p = 0.4375 | |
| Control RAPA n = 17 vs mutant RAPA n = 21 | p = 0.1367 | |
| Control VEH n = 13 vs control RAPA n = 17 | p > 0.9999 | |
| Mutant VEH n = 11 vs mutant RAPA n = 21 | p > 0.9999 | |
| Figure 2, cell survival | ||
| Cell count | ||
| Two-way ANOVA | ||
| ANOVA table | p value | F (DFn,DFd) |
| Interaction | p < 0.0001 | F(1,11) = 38.68 |
| Treatment | p < 0.0001 | F(1,11) = 53.47 |
| Genotype | p < 0.0001 | F(1,11) = 103.0 |
| 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 = 0.0547 | |
| Control VEH n = 4 vs control RAPA n = 4 | p = 0.8911 | |
| Mutant VEH n = 3 vs mutant RAPA n = 3 | p < 0.0001 | |
| Mutant VEH n = 3 vs control RAPA n = 4 | p < 0.0001 | |
| Figure 3, physiology | ||
| PC intrinsic firing rate | ||
| Two-way ANOVA | ||
| ANOVA table | p value | F (DFn,DFd) |
| Interaction | p = 0.0225 | F(1,142) = 5.320 |
| Treatment | p = 0.0026 | F(1,142) = 9.406 |
| Genotype | p = 0.0001 | F(1,142) = 15.54 |
| Bonferroni's multiple comparisons test | Adjusted p value | |
| Control VEH n = 45 vs mutant VEH n = 36 | p < 0.0001 | |
| Control RAPA n = 30 vs mutant RAPA n = 35 | p = 0.5465 | |
| Control VEH n = 45 vs control RAPA n = 30 | p > 0.9999 | |
| Mutant VEH n = 36 vs mutant RAPA n = 35 | p = 0.0005 | |
| Mutant VEH n = 36 vs control RAPA n = 30 | p < 0.0001 | |
| PC evoked responses | ||
| Two-way ANOVA | ||
| ANOVA table | p value | F (DFn,DFd) |
| Interaction | p < 0.0001 | F(87,1852) = 2.112 |
| Current step | p < 0.0001 | F(29,1852) = 100.9 |
| Group | p < 0.0001 | F(3,1852) = 313.6 |
| Bonferroni's multiple comparisons test | Adjusted p value | |
| Control VEH n = 13 vs mutant VEH n = 10 | p < 0.0001 | |
| Control RAPA n = 29 vs mutant RAPA n = 14 | p < 0.0001 | |
| Control VEH n = 13 vs control RAPA n = 29 | p = 0.0255 | |
| Mutant VEH n = 10 vs mutant RAPA n = 14 | p = 0.0075 | |
| Mutant VEH n = 10 vs control RAPA n = 29 | p < 0.0001 | |
| Membrane input resistance | ||
| Two-way ANOVA | ||
| ANOVA table | p value | F (DFn,DFd) |
| Interaction | p = 0.8539 | F(1,86) = 0.03412 |
| Treatment | p = 1.127 | F(1,86) = 1.254 |
| Genotype | p < 0.0001 | F(1,86) = 18.67 |
| Bonferroni's multiple comparisons test | Adjusted p value | |
| Control VEH n = 12 vs mutant VEH n = 17 | p = 0.0283 | |
| Control RAPA n = 34 vs mutant RAPA n = 27 | p = 0.0003 | |
| Control VEH n = 12 vs control RAPA n = 34 | p = 0.7549 | |
| Mutant VEH n = 17 vs mutant RAPA n = 27 | p = 0.9845 | |
| Mutant VEH n = 17 vs control RAPA n = 34 | p = 0.0004 | |
| Membrane capacitance | ||
| Two-way ANOVA | ||
| ANOVA table | p value | F (DFn,DFd) |
| Interaction | p = 0.9078 | F(1,23) = 0.01373 |
| Treatment | p = 0.9270 | F(1,23) = 0.008569 |
| Genotype | p = 0.7735 | F(1,23) = 0.08483 |
| Membrane time constant | ||
| Two-way ANOVA | ||
| ANOVA table | p value | F (DFn,DFd) |
| Interaction | p = 0.2842 | F(1,23) = 1.203 |
| Treatment | p = 0.5662 | F(1,23) = 0.3388 |
| Genotype | p = 0.0022 | F(1,23) = 11.86 |
| Bonferroni's multiple comparisons test | Adjusted p value | |
| Control VEH n = 6 vs mutant VEH n = 6 | p = 0.0114 | |
| Control RAPA n = 8 vs mutant RAPA n = 7 | p = 0.1840 | |
| Control VEH n = 6 vs control RAPA n = 8 | p > 0.9999 | |
| Mutant VEH n = 6 vs mutant RAPA n = 7 | p = 0.5081 | |
| Mutant VEH n = 6 vs control RAPA n = 8 | p = 0.0496 | |
| Mouse age at time of testing (all experiments) | ||
| 8-week treatment paradigm | ||
| Rotarod | 13 weeks | Rotarod |
| Open field | 14 weeks | Open field |
| Elevated plus maze | 14 weeks | Elevated plus maze |
| Social interaction (three-chamber) | 15 weeks | Social interaction (three-chamber) |
| Social olfaction | 15 weeks | Social olfaction |
| Grooming | 15 weeks | Grooming |
| Water Y maze | 16 weeks | Water Y maze |
| Immunohistochemistry | 13–16 weeks | Immunohistochemistry |
| Acute slice physiology | 13–16 weeks | Acute slice physiology |