Article Figures & Data
Figures
- Figure 1.
Recording sites and raw data examples of simultaneous recordings of LFPs in the awake mouse mPFC and hippocampal CA1 region. A, Schematic drawing of the top view of a mouse brain. LFPs were simultaneously recorded from the left PFC along the boundary between the frontal association area and prelimbic cortex (blue dots) and S1/V1 transition area (red dots). The electrodes in S1/V1 (red dots) were advanced into the CA1 region of the hippocampus following recording in S1/V1. The green dot represents bregma. Dashed lines represent the coronal sections for verifying recording locations in the mPFC and CA1 in a mouse not included in this study but recorded following identical procedures (see Materials and Methods). B, Electrolytic lesions (arrows) in the mPFC (left) and the CA1 region of hippocampus (right) marking sites from which recordings shown in C were obtained. C, Examples of raw LFP data recorded at sites indicated in A. LFP1 and LFP2 were recorded from electrodes positioned in the mPFC (blue); LFP3 and LFP4 were recorded from electrodes in the CA1 (red). Arrow points at a characteristic high-frequency ripple activity. Abscissa represents time in seconds. D, An enlarged view of raw LFPs around a hippocampal ripple event (arrow). Same LFP amplitude scale bar as in C. E, High-pass filtered versions of the LFPs in panel D emphasizes the high-frequency ripple components of CA1 activity. Horizontal dashed line above LFP3 represents the mean filtered LFP amplitude plus 4 SD from a continuous data of 60 s, which was used as a threshold (mean ± 4 SD) for automatic detection of SWR activity in the CA1 region. Left and right arrows mark the beginning and the end of ripple activity, respectively.
- Figure 2.
Coherence in the LFP oscillation in mice with mTBI. A, mPFC. *F(2,24) = 5.2474, p = 0.0129; sham + VEH versus mTBI + VEH: p = 0.0499. ▲F(2,24) = 3.4297, p = 0.0490; sham + VEH versus mTBI + VEH: p = 0.0411. B, S1/V1. *F(2,24) = 4.1190, p = 0.0337; sham + VEH versus mTBI + VEH: p = 0.0326. C, Hippocampal CA1 region. The same color codes are used for all panels. Data were expressed as mean ± SE. Comparisons of mean coherence between 4 and 30 Hz were conducted using one-way ANOVA (post hoc test: Tukey-Kramer). VEH, vehicle.
- Figure 3.
Time-frequency analysis of ripple activity in the hippocampal CA1 region. A, Time-frequency mapping of LFP around CA1 ripples. Data are aligned on the onset of ripple activity (at time 0 s). Color represents frequency power normalized to the maximal power in the three groups. The white cross that is centered at the peak-frequency-power represents mean ± SD of the peak-power times (abscissa) and peak frequencies (ordinate) of ripple activities. B, C, Comparisons of peak frequency B and frequency power of ripple activity C. Data are expressed as mean ± SE. One-way ANOVA (post hoc test: Tukey-Kramer) for peak frequency in B: F(2,24) = 12.6401, p = 0.0463; *p = 0.0159; **p = 0.0001. VEH, vehicle.
- Figure 4.
Changes in the amplitude of LFP in the mPFC during hippocampal ripple activities. A, B, LFPs recorded in the mPFC and hippocampal CA1 region, respectively. Data are aligned on the onset of the hippocampal ripples (t = 0 s). One-way ANOVA (post hoc test: Tukey-Kramer): *F(2,24) = 3.5031, p = 0.0463; sham + VEH versus mTBI + VEH: p = 0.0456. ▲F(2,24) = 4.0177, p = 0.0313; sham + VEH versus mTBI + drug: p = 0.0489. VEH, vehicle.
- Figure 5.
θ Oscillatory phase modulates γ-band LFP activity in mice with mTBI. A, PAC mapping of LFP activity in the mPFC. PAC values (color-coded) are normalized to the maximum value found within the three experimental groups within each region. B, PAC mapping of LFP activity in CA1. The same method for data-normalization as in A was used. C, Line-graph representations of PAC in the mPFC for each experimental condition, shown separately for the low γ (low γ, left panel) and high γ (high γ, right panel) frequency ranges. Data are expressed as mean ± SE. One-way ANOVA (post hoc test: Tukey-Kramer): *F(2,24) = 2.8977, p = 0.0746; sham + VEH versus mTBI + VEH: p = 0.0604. ▲F(2,24) = 3.0115, p = 0.0681; sham + VEH versus mTBI + drug: p = 0.0759. D, Same analysis as in panel C but for the hippocampal CA1 region. Same data legends as in C. Norm. Mod. Index, normalized modulation index; VEH, vehicle.
- Figure 6.
Effects of vehicle (VEH, blue traces) and SMM-189 (drug, red traces) treatment on neuronal activity in sham-treated control mice. A, Coherence of LFP in hippocampal CA1 region (CA1) in drug and vehicle-treated sham mice. B, Coherence of LFP in the mPFC. C, Average SWR wave form in CA1 in drug and vehicle-treated mice. D, Average LFP responses in the mPFC aligned with SWR onset in drug and vehicle-treated mice. E, F, Time-frequency mapping of SWR activity in CA1 in drug and vehicle-treated mice. Time 0 corresponds to SWR onset. Pseudocolors represent frequency power normalized to the maximum power (Norm. Power) within both groups. G, H, Quantitative representation and comparison of peak frequency (G) and normalized peak power (H) of SWR activity shown in panels E, F. Statistical comparison (one-way ANOVA) of all quantitative endpoints between drug versus vehicle-treated mice revealed no differences between the two groups in any of the measures.
Tables
- Table 1.
Summary of effects of SMM-189 on LFP and hippocampal SWR activity in mice with mTBI
CA1 mPFC S1/V1 Sham + drug mTBI + VEH mTBI + drug Sham + drug mTBI + VEH mTBI + drug Sham + drug mTBI + VEH mTBI + drug LFP power spectrum Same as sham + VEH Same as sham + VEH Same as sham + VEH Same as sham + VEH Same as sham + VEH Same as sham + VEH Same as sham + VEH Same as sham + VEH Same as sham + VEH LFP coherence within area Same as sham + VEH ↑ Same as sham + VEH Same as sham + VEH Same as sham + VEH Same as sham + VEH Same as sham + VEH ↑ ↑ LFP coherence with CA1 N/A N/A N/A Same as sham + VEH Same as sham + VEH Same as sham + VEH N/A N/A N/A LFP coherence with S1/V1 N/A N/A N/A Same as sham + VEH Same as sham + VEH Same as sham + VEH N/A N/A N/A SWR frequency Same as sham + VEH ↓ Same as sham + VEH N/A N/A N/A N/A N/A N/A SWR relative frequency power Same as sham + VEH Same as sham + VEH Same as sham + VEH N/A N/A N/A N/A N/A N/A SWR-associated LFP amplitude Same as sham + VEH Same as sham + VEH ↑ Same as sham + VEH ↓ Same as sham + VEH N/A N/A N/A θ-γ coupling N/A Same as sham + VEH Same as sham + VEH N/A ↑ Same as sham + VEH N/A N/A N/A CA1, hippocampal CA1 region; N/A, not applicable; VEH, vehicle; ↑, increase; ↓ , decrease.
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