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. 2021 Jun 16;12:3653. doi: 10.1038/s41467-021-23939-7

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 10 — a Schematic for treatment paradigm. b–g Representative immunostained sections of somatosensory cortex labeled for PV (green) and gephyrin (red) in Vehicle (b–d) and Rapamycin (e–g) treated mice showing PV-Gephyrin colocalized boutons (arrowheads). h PV-Gephyrin colocalized puncta in Vehicle (one-way Anova, *p = 0.036; Tukey’s multiple comparisons test: Tsc1^Ctrl vs PV-Cre; Tsc1^flox/+ *p = 0.0401; Tsc1^Ctrl vs PV-Cre; Tsc1^flox/flox *p = 0.0281, PV-Cre; Tsc1^flox/+ vs PV-Cre;Tsc1^flox/flox *p = 0.9942) and i Rapamycin treated mice (one-way Anova, p = 0.7355; Tukey’s multiple comparisons test: Tsc1^Ctrl vs PV-Cre;Tsc1^flox/+ p = 0.8421; Tsc1^Ctrl vs PV-Cre; Tsc1^flox/flox p = 0.7298, PV-Cre; Tsc1^flox/+ vs PV-Cre; Tsc1^flox/flox p = 0.9774). Number of vehicle-treated mice: Tsc1^Ctrl, n = 3; PV-Cre; Tsc1^flox/+, n = 4; PV-Cre; Tsc1^flox/flox, n = 5. Number of rapamycin treated mice: n = 5 for all the genotypes. j Open field test. Vehicle-treated mice: Tsc1^Ctrl, n = 10; PV-Cre;Tsc1^flox/+, n = 7; PV-Cre;Tsc1^flox/flox, n = 5. Rapamycin-treated mice: Tsc1^Ctrl, n = 17; PV-Cre;Tsc1^flox/+, n = 10; PV-Cre;Tsc1^flox/flox, n = 10. k Elevated plus maze test. Vehicle-treated mice: Tsc1^Ctrl, n = 16; PV-Cre; Tsc1^flox/+, n = 7; PV-Cre;Tsc1^flox/flox, n = 9; Rapamycin-treated mice: Tsc1^Ctrl, n = 17; PV-Cre;Tsc1^flox/+, n = 11; PV-Cre;Tsc1^flox/flox, n = 11. l, m Rapamycin treatment from P14-21 rescues social approach (l, two-way ANOVA vehicle, F_genotype (2, 20) = 1.615 p = 0.2238, F_time (1, 20) = 4.789 p = 0.0407, F_{genotype*time} (2, 20) = 3.395 p = 0.0538; *p = 0.0230, Holm–Sidak’s multiple comparisons test. Two-way ANOVA rapamycin, F_genotype (2, 29) = 1.027 p = 0.3709, F_time (1, 29) = 22.08 p < 0.0001, F_{genotype*time} (2, 29) = 4.580 p = 0.0187; **p = 0.0019, ***p = 0.0002, Holm-Sidak’s multiple comparisons test) and social novelty deficits (m, two-way ANOVA vehicle, F_genotype (2, 20) = 0.8281 p = 0.4513, F_time (1, 20) = 5.876 p = 0.0250, F_{genotype*time} (2, 20) = 6.036 p = 0.0089; **p = 0.0053, Holm–Sidak’s multiple comparisons test. Two-way ANOVA rapamycin, F_genotype (2, 29) = 0.4667 p = 0.6317, F_time (1, 29) = 18.84 p = 0.0002, F_{genotype*time} (2, 29) = 0.09351 p = 0.9110; **p = 0.0081, *p = 0.0336, Holm–Sidak’s multiple comparisons test) in PV-Cre; Tsc1^flox/+, but not in PV-Cre;Tsc1^flox/flox mice. Vehicle-treated mice: Tsc1^Ctrl, n = 7; PV-Cre; Tsc1^flox/+, n = 9; PV-Cre;Tsc1^flox/flox, n = 7. Rapamycin-treated mice: Tsc1^Ctrl, n = 14; PV-Cre;Tsc1^flox/+, n = 10; PV-Cre;Tsc1^flox/flox, n = 8. Scale bar: 5 µm. Data represent mean ± SEM. Source data are provided as a Source Data file.