Figure 1. Impaired spatial memory is associated with aberrant CA1 network oscillations and theta-gamma phase-amplitude coupling in 7- to 8-month-old rTg4510 mice. a, Hidden platform and probe task performance in the Morris water maze in WT (n = 10) and rTg4510 (n = 10) mice. The maze consisted of a 1-m-diameter circular pool filled with opacified water and was surrounded by overt visual cues. A 9-cm-diameter escape platform was concealed ∼1 cm beneath the water in one of the four maze quadrants. The length of swim path required to locate the escape platform was measured within a 60 s time limit and averaged across four consecutive trails (30 s intertrial interval). The probe trial was performed on day 8. The escape platform was removed, and the length of swim path spent searching the target maze quadrant was measured within a 30 s time limit. Dashed line plots the chance performance level (25% path length inside target maze quadrant). b, Photomicrographs of Nissl-stained coronal brain sections illustrating recording positions (arrows) in the CA1-PN layer in a representative WT and rTg4510 mouse. c, d, The 5 s traces of raw LFP recorded in the CA1-PN layer of a representative WT (c) and rTg4510 (d) mouse. Expanded traces of wideband (W, 1–200 Hz), theta (θ, red, 4–12 Hz), and gamma (γ, green, 25–120 Hz) LFPs are plotted below. In the WT traces (c), peaks in gamma amplitude coincide with peaks in the theta cycle, an example of theta-gamma PAC. e, Periodogram illustrating the wideband power spectral density (PSD) of CA1 LFPs in WT and rTg4510 mice. Inset, Plot of the 1–20 Hz PSD. f, Total PSD (integral of periodogram) for discrete frequency bands of CA1 network oscillations in WT and rTg4510 mice: delta (δ; 1–4 Hz); theta (θ); beta (β; 12–25 Hz); slow gamma (γS; 25–50 Hz); fast gamma (γF; 50–120 Hz); high-frequency oscillations (HFO; 120–200 Hz). g, Relative PSD (% wideband power) for discrete frequency bands of CA1 network oscillations in WT and rTg4510 mice. h, i, Population-averaged comodulograms illustrating theta-gamma PAC in WT CA1 LFPs (h) and strong attenuation of theta-gamma PAC in rTg4510 CA1 LFPs (i). j, Quantification of theta-gamma PAC. e–g, h, Data are mean ± SEM from n = 6 WT and n = 7 rTg4510 mice. *p < 0.05. ***p < 0.005.