Fig. 1: Chronically stressed mice exhibited increased functional brain connectivity in the BNST and NAc.

a Protocol used for unpredictable chronic mild stress (UCMS) and functional brain connectivity measurement and paradigm for behavioral assay. b Left, representative mouse trajectory map for both naive (n = 9 mice) and stressed groups (n = 15 mice) in the open field test (OFT), warm colors represent high time spent; middle, time spent in central compartment; right, average velocity in the OFT (Unpaired t test, middle, t = 2.401, P = 0.0241; right, t = 1.591, P = 0.1241). c Left, representative mouse trajectory map in the elevated plus maze (EPM), middle, time spent in the open arms; right, open-arm entries; (Unpaired t test, middle, t = 7.145, P < 0.0001; right, t = 3.214, P = 0.0040). d Left serum CRH and right NE concentrations of naive control (n = 6 mice) and stressed groups (n = 8 mice) (Unpaired t test, left, t = 2.671, P = 0.0204; right, t = 5.865, P < 0.0001). e Correlation matrices derived from global fMRI BOLD signal analysis (pseudocolor map of t statistics after thresholding at a false discovery rate, P of 0.05) across brain regions in stressed compared with wild-type naive littermates; warm colors represent higher correlations. f Difference in functional connectivity between stressed and naive littermate groups. Red, naive > stress; blue, naive < stress, *significant difference (t test, BNST-NAc: t = −2.69812, P = 0.010777; BNST-Amy: t = −3.14356, P = 0.003453; PAG-HIP: t = 2.315667, P = 0.026741). g Correlation of BOLD synchronization in BNST-NAc in stressed (n = 7 mice) and naive littermates (n = 5 mice) (Unpaired t test, t = 2.698, P = 0.0108). h Schematic showing local field potential recording strategy. i Coherence between LFP signals recorded from NAc and BNST in stressed (n = 7 mice) and naive control mice (n = 7 mice). j Coherence in theta (4–12 Hz), beta (12–30 Hz) and low gamma (30–50 Hz) bands in NAc and BNST (Unpaired t test, theta: t = 2.065, P = 0.0440, beta: t = 2.584, P = 0.0126, low gamma: t = 2.856, P = 0.0061). k–l Sum of power spectra obtained for LFP recordings in NAc shell (Mann–Whitney rank sum test, theta: P = 0.0058, beta: P = 0.8662, low gamma: P = 0.6395) and BNST (Mann–Whitney rank sum test, theta: P = 0.004, beta: P = 0.5867, low gamma: P = 0.5867). *P < 0.05, **P < 0.01 and ***P < 0.0001. Error bars (c, d, g, j–l) are mean ± SEM. In i, the curves and shaded areas indicate the mean ± SEM.