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. 2021 Oct 19;12:6084. doi: 10.1038/s41467-021-26131-z

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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. 3 — a Experimental design of spine density measurements (left). Developmental treatment with the mTOR inhibitor rapamycin normalized dendritic spine density in rapamycin-treated Tsc2^+/− mice (+/− rapa) to the level of vehicle-treated Tsc2^+/+ control mice (+/+). n = 7 mice (+/+, +/− rapa, and +/+ rapa) and n = 5 mice (+/−). b Voxelwise rsfMRI mapping showed a pattern of decreased long-range functional connectivity in rapamycin-treated Tsc2^+/− mice (blue), recapitulating the anatomical regions showing increased rsfMRI connectivity in Tsc2^+/− mice (red–yellow coloring, left). Rescue here denotes the effect of rapamycin in Tsc2^+/− mutants i.e., areas of decreased rsfMRI connectivity in rapamycin-treated vs. vehicle-treated Tsc2^+/− mice. Global histogram analysis confirmed the rescue of long-range hyperconnectivity in prefrontal and insular regions of rapamycin-treated mutants (right). c Spatial extension of the mouse default-mode network in the vehicle- (top) and rapamycin- (bottom) treated Tsc2^+/− mice. Between-group connectivity mapping and regional quantifications revealed that treatment with rapamycin rescued prefrontal rsfMRI hyperconnectivity in Tsc2^+/− mice to levels comparable to control mice (right). n = 20 mice for each group. d Spatial extension of the salience network in the vehicle- (top) and rapamycin- (bottom) treated Tsc2^+/− mice. Rapamycin completely rescued salience network hyperconnectivity in rapamycin-treated Tsc2^+/− mice. Rescue in (c) and (d) denotes the effect of rapamycin in Tsc2^+/− mutants i.e., areas of decreased rsfMRI connectivity in rapamycin-treated vs. vehicle-treated Tsc2^+/- mice. n = 20 mice for each group. e Rapamycin also rescued altered self-grooming and social behaviors in Tsc2^+/− rapa mice. Grooming, mice, n = 20 (+/+), n = 20 (+/−), n = 19 (+/+ rapa), n = 19 (+/− rapa). Social investigation, mice, n = 20 (+/+), n = 20 (+/−), n = 15 (+/+ rapa), n = 19 (+/− rapa). f Voxelwise correlation mapping revealed a significant positive correlation between prefrontal (left, Pearson’s r, r = 0.351, P = 0.002) and insular (right, Pearson’s r, r = 0.415, P < 0.001) rsfMRI connectivity, and motor stereotypes. PFC prefrontal cortex, CPu striatum, RS retrosplenial cortex, Ins insular cortex. Scatterplots represent the quantification of these correlations in the striatum and PFC, respectively. *q < 0.05, **q < 0.01, all FDR-corrected. Error bars represent SEM. Source data are provided as a Source Data file.