Stress enhances hippocampal neuronal synchrony and alters ripple-spike interaction - PubMed (original) (raw)

Fig. 1

CA1 pyramidal cell activity is altered during stress. (A) Schematic representation of the chronic immobilization stress (CIS) protocol that mice received every day for 10 consecutive days. (B) Coronal section of the hippocampus showing the tetrode locations (black arrows) at the CA1 pyramidal layer. (C) Time matched (30 min) representative examples of unsorted spikes recorded during rest-state (left) and stress-state (right). Numbers next to each cluster depict total number of spikes recorded during that state. (D) Mean firing rate between rest-state and stress-state (two-way ANOVA: behaviour-state, F(1, 1074) = 65.801, p = 1.35 × 10−15; day, F(1, 1074) = 0.183, p = 0.669; behavior-state x day interaction, F(1,1074) = 6.246, p = 0.013; Tukey's HSD: acute-rest vs acute-stress, p = 9.49 × 10−13; acute-rest vs chronic-rest, p = 0.095; chronic-rest vs chronic-stress, p = 0.0012). (E) Peak firing rate between rest-state and stress-state (two-way ANOVA: behavior-state, F(1, 1074) = 142.510, p < 2.224 × 10−16; day, F(1, 1074) = 2.971, p = 0.085; behaviour-state x day interaction, F(1, 1074) = 0.817, p = 0.366; Tukey's HSD: acute-rest vs acute-stress, p = 6.41 × 10−13; chronic-rest, vs chronic-stress, p = 1.38 × 10−12). (F) Inter-burst-interval between rest-state and stress-state (two-way ANOVA: behaviour-state, F(1, 1066) = 73.572, p < 2.22 × 10−16; day, F(1, 1066) = 0.011, p = 0.916; behaviour-state x day interaction, F(1, 1066) = 4.798, p = 0.029; Tukey's HSD: acute-rest vs acute-stress, 2.84 × 10−13; chronic-rest vs chronic-stress, p = 1.22 × 10−4). (G) Correlation between theta/delta ratio and SPW-Rs differs between behaviour-states on the first day (left: acute-rest, slope = −0.044, R = −0.56, p = 0.02; acute-stress, slope = 0.00, R = −0.19, p = 0.47) and last day (right: chronic-rest, slope = −0.04, R = −0.54, p = 0.029; chronic-stress, slope = −0.01, R = −0.17, p = 0.52) of CIS. All box plots represent interquartile range (IQR, 25th-75th percentiles), median is the thick line in the box and whiskers extend to 1.5 times the IQR. Circles depict rest-state (black) stress-state (red). *p < 0.05, **p < 0.01, ***p < 0.001. acute-rest: n = 288 cells, N = 17 mice, acute-stress: n = 282 cells, N = 16 mice, chronic-rest: n = 282 cells, N = 16 mice, chronic stress: n = 226 cells, N = 16 mice). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2

CA1 SPW-R duration differs between rest and stress states. (A) Representative examples of local field potential (LFP) for non-filtered (top) and filtered (bottom) SPW-R events recorded during rest-state (left) and stress-state (right) from CA1 stratum pyramidale. (B) SPW-R duration differs between rest-state and stress-state; (two-way ANOVA: behaviour-state, F(1, 61) = 34.035, p = 2.22 × 10−7; day, F(1, 61) = 0.419, p = 0.520; behaviour-state x day, F(1, 61) = 1.813, p = 0.183; Tukey's HSD: acute-rest vs acute-stress, p = 2.07 × 10−5, chronic-rest vs chronic-stress, p = 0.0137). (C) Distributions of the duration of SPW-Rs differs between behaviour states on first day (left: acute-rest vs acute-stress, Kolmogorov-Smirnov test, D = 0.236, p < 2.22 × 10−16) and last day (right: chronic-rest vs chronic-stress, Kolmogorov-Smirnov test, D = 0.113, p < 2.22 × 10−16) showed a rightward shift. Dotted vertical lines represent median values. (D) Temporal dynamics of averaged SPW-R duration (1-min bins) differ between behaviour states on the first day (left: LMMs; behaviour-state, F(1, 447) = 290. 40, p < 2.22 × 10−16; time, F(14, 447) = 0.757, p = 0.716; behaviour-state x time, F(14, 447) = 0.447, p = 0.958). Similarly, on the last day, SPW-R duration increased during stress (right: LMMs; behaviour-state, F(1, 412) = 94.08, p < 2.22 × 10−16; time: F(14, 412) = 1.19, p = 0.276; behaviour-state x time, F(14, 412) = 0.631, p = 0.839). (E) Averaged peri-SPW-R wavelet spectrograms during acute-rest (top left), acute-stress (bottom left), chronic-rest (top right) and chronic-stress (bottom right). (F) Low gamma (17–40Hz) power during SPW-R events does not differ between behaviour-states (two-way ANOVA: behaviour-state, F(1, 61) = 0.80, p = 0.38; day, F(1, 61) = 0.008, p = 0.928; behaviour-state x day, F(1, 61) = 0.105, p = 0.75). (G) Fraction of different types of ripple bursts during acute stress (two-way ANOVA: behaviour-state, F(1, 124) = 0.374, p = 0.542; category, F(3, 124) = 156.68, p < 2.22 × 10−16; behaviour-state x category, F(3, 124) = 0.211, p = 0.89; Tukey's HSD: acute-rest vs acute-stress: singlets, p = 0.999; doublets, p = 0.998; triplets, p = 0.999; others, p = 0.996) and chronic stress (two-way ANOVA: behaviour-state, F(1, 120) = 0.068, p = 0.795; category, F(3, 120) = 147.2, p < 2.22 × 10−16; behaviour-state x category, F(3, 124) = 0.371, p = 0.774; Tukey's HSD: chronic-rest vs chronic-stress: singlets, p = 1.0; doublets, p = 0.999; triplets, p = 0.967; others, p = 1.0). All box plots represent median and 25th-75th percentiles, with whiskers extending to the extreme data points. Circles depict rest-state (black) stress-state (red). *p < 0.05, **p < 0.01, ***p < 0.001. Acute-rest: n = 7220 SPW-Rs, N = 17 mice; acute-stress: n = 9851 SPW-Rs, N = 16 mice; chronic-rest: n = 7041 SPW-Rs, N = 16 mice; chronic stress: n = 8978 SPW-Rs, N = 16 mice). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 3

Altered CA1 pyramidal activation in SPW-Rs during stress-state. (A) The relationship between SPW-R duration (20-ms bins) and multiunit activity during SPW-Rs for first (left) and last (right) day of CIS (LMMs: behaviour-state, F(1, 16896) = 578.48, p < 2.22 × 10−16; duration, F(16, 16896) = 474.38, p < 2.22 × 10−16; behaviour-state x duration, F(16, 16896) = 1.955, p = 0.162) and the last day (LMMs: behaviour-state, F(1, 15877) = 1383.89, p < 2.22 × 10−16; duration, F(16, 15877) = 358.20, p < 2.22 × 10−16; behaviour-state x day, F(16, 15877) = 8.954, p<=0.003) of CIS). Green dots on top of graph indicate significant differences between behaviour-states. (B) Within SPW-R average firing rate differs between behaviour-states (two-way ANOVA: behavior-state, F(1, 1074) = 21.262, p = 4.49 × 10−6; day, F(1, 1074) = 1.037, p = 0.309; behaviour-state x day, F(1, 1074) = 8.552, p = 0.003; acute-rest vs acute-stress, p = 5.97 × 10−7; chronic-rest vs chronic-stress, p = 0.736; acute-rest vs chronic-rest, p = 0.019). (C) Percentage of spikes discharged by CA1 pyramidal cells in SPW-R differs between behaviour-states (two-way ANOVA: behaviour-state, F(1, 1074) = 84.83, p < 2.22 × 10−16; day F(1, 1074) = 0.079, p = 0.778; behaviour-state x day, F(1, 1074) = 1.35, p = 0.25; Tukey's HSD: acute-rest vs acute-stress, p = 1.4 × 10−12; chronic-rest vs chronic-stress, p = 3.62 × 10−7). (D) Dependency of pyramidal cell participation in SPW-Rs on their mean firing rate on the first day (acute-rest: slope = 0.848, R2 = 0.55, p < 2.22 × 10−16; acute-stress: slope = 0.96, R2 = 0.40, p < 2.22 × 10−16; likelihood-ratio test (df = 1) = 4.318, p = 0.038) and the last day (chronic-rest: slope = 0.903, R2 = 0.42, p < 2.22 × 10−16; chronic-stress: slope = 0.898, R2 = 0.21, p = 2.97 × 10−13; likelihood-ratio test (df = 1) = 0.006, p = 0.94) of CIS. (E) Pyramidal cell participation in SPW-Rs differs with the progression of stress protocol (two-way ANOVA: behaviour-state, F(1, 1074) = 1.614, p = 0.204; day, F(1, 1074) = 4.951, p = 0.026; behaviour-state x day, F(1, 1074) = 1.967, p = 0.161; Tukey's HSD: acute-rest vs acute-stress, p = 0.235; chronic-rest vs chronic-stress, p = 0.999; acute-rest vs chronic-rest, p = 0.043). (F) Cumulative distribution of pyramidal cell participation in SPW-Rs differs between rest-states on the first day (black) and last day (blue) of CIS (Kolmogorov-Smirnov test: D = 0.142, p = 0.006). All box-plots, represent interquartile range (IQR, 25th-75th percentiles), median is the thick line in the box and whiskers extend to 1.5 times the IQR. *p < 0.05, **p < 0.01, ***p < 0.001. Acute-rest: n = 288 cells, N = 17 mice; acute-stress: n = 282 cells, N = 16 mice; chronic-rest: n = 282 cells, N = 16 mice; chronic stress: n = 226 cells, N = 16 mice). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

Altered CA1 pyramidal cell coactivation in SPW-Rs during stress-state. (A) Co-activity Z-scores of pyramidal cells during SPW-Rs differ between rest-state (black) and stress-state (red) (two-way ANOVA: behaviour-state, F(1, 6195) = 41.286, p = 1.41 × 10−10; day, F(1, 6195) = 4.676, p = 0.031; behaviour-state x day, F(1, 6195) = 4.861, p = 0.027; Tukey's HSD: acute-rest, n = 1625 cell pairs vs acute-stress, n = 1610 cell pairs, p = 4.04 × 10−9; chronic-rest, 1701 cell pairs vs chronic-stress, n = 1263 cell pairs, p = 0.025; acute-rest vs chronic-rest, p = 0.0035). (B) Relationship between cell pairs of positive co-activity Z-scores during both rest-state and stress-state significantly differs between days (acute: slope = 0.99, R2 = 0.022, p = 0.033 n = 208 cell pairs; chronic: slope = 1.74, R2 = 0.019, p = 0.076, n = 165 cell pairs; likelihood-ratio test, p = 1.28 × 10−7) of CIS. (C) Group histograms for pyramidal cell spiking during SPW-Rs for acute-rest (grey), acute-stress (green), chronic-rest (red) and chronic-stress (maroon). The Blue lines on each subpanel represents the phase of the SPW-R. (D) Modulation index differs slightly between days (LMMs: behaviour-state, F(1, 311) = 0.016, p = 0.900; day, F(1,311) = 6.335, p = 0.012; behaviour-state x duration, F(1, 311) = 1.294, p = 0.256; Tukey's HSD: acute rest vs chronic rest, p = 0.049). Boxplots represent interquartile range (IQR, 25th-75th percentiles), median is the thick line in the box and whiskers extend to 1.5 times the IQR. *p < 0.01, **p < 0.005, ***p < 0.001. Acute-rest: N = 17 mice; acute-stress, N = 16 mice; chronic-rest, N = 16 mice; chronic-stress, N = 16 mice). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)