a, Mouse in virtual reality environment. b, LFP recorded in CA1, above, filtered for theta (left) or SWRs (right), middle, and gamma, below. c, Mean and standard deviation of the normalized power spectrum during theta. Each animal’s power spectral density was normalized to its peak (n = 6 mice per group). d, Normalized power spectral densities during theta periods in 3-month-old 5XFAD (green, n = 6 mice) and WT (black/grey, n = 6 mice) mice. Each animal’s power spectral density was normalized to its peak (in theta). e, Average SWR-triggered spectrograms for one WT and one 5XFAD mouse shows an increase in the gamma band during SWRs. This increase is lower in the 5XFAD mouse than in the WT mouse (n = 370 and 514 SWRs in WT and 5XFAD, respectively; WT mouse shown here is the same as in Fig. 1a). This range of frequencies is often called ‘slow gamma’ to distinguish it from faster oscillations (65–140 Hz) that have also been included in the gamma range but for which the origins are less well understood. f, Distributions for each recording (left) and the mean and standard error across sessions (right) of instantaneous gamma frequencies during SWRs in 5XFAD (green) and WT (black) mice show distributions around 40 Hz (n = 820, 800, 679, 38, 1,875, 57 gamma cycles per session in six 5XFAD animals in six recording sessions and 181, 1,075, 919, 1,622, 51, 1,860, 1,903 gamma cycles per session in six WT animals in seven recording sessions). g, Cumulative distribution of the z-scored gamma power during the 100 ms around the peak of the SWR for WT (black) and 5XFAD animals (green) for each animal (left) and the mean and standard error (shaded) across animals (right) (n = 514, 358, 430, 22, 805, 37 SWRs per session in six 5XFAD animals and 82, 311, 370, 776, 18, 710, 818 SWRs per session in six WT animals). h, Fraction of spikes in CA1 during SWRs as a function of the phase of gamma in 5XFAD (green) and WT (black) mice for each animal (left) and the mean and standard error across animals (right, n = 2475, 1060, 3092, 25, 6521, 123 spikes during SWRs per session in six 5XFAD mice and 360, 4741, 1,564, 2,961, 88, 3,058, 4,270 spikes during SWRs per session in six WT mice). i, SWR rate per non-theta period in 5XFAD (green) and WT (black) mice for each animal (left) and all animals combined (right, rank-sum test, P < 10−10, n = 117, 210, 151, 55, 100, 1 non-theta periods per session in six 5XFAD mice and 80, 68, 115, 95, 15, 159, 218 non-theta periods per session in six WT mice). j, The cumulative distribution of gamma power during large SWRs (detection threshold greater than six standard deviations above the mean, Methods) shows significantly smaller increases in 5XFAD (green) than WT (black) mice (rank-sum test, P < 10−5, n = 1,000 SWRs in six 5XFAD mice and 1,467 SWRs in 6 WT mice). k, Fraction of spikes as a function of the phase of gamma during large SWRs (detection threshold greater than six standard deviations above the mean, Methods), mean ± s.e.m. (left) and histogram of the depth of modulation of spiking (right) as a function of gamma phase in 3-month-old 5XFAD (green, n = 6 mice) and WT (black, n = 6 mice) mice (rank-sum test, bootstrap resampling P < 10−10, n = 2500 5XFAD spike-gamma phase distributions and 3,000 WT distributions). l, Power spectral density during 40 Hz stimulation (red, left), random stimulation (blue, centre), or no stimulation (black, right) of FS-PV-interneurons in CA1 for each mouse (n = 4 5XFAD mice with 169, 130, 240, 73 40 Hz, 143, 129, 150, 72 random, and 278, 380, 52, 215 no stimulation periods per animal and n = 3 WT mice with 65, 93, 91 40 Hz, 64, 93, 90 random, and 187, 276, 270 no stimulation periods per animal). m, Above: example raw LFP trace (above) and the trace filtered for spikes (300–6,000 Hz, below), with spikes indicated with red stars after optogenetic stimulation (blue vertical lines). Below: histogram of spikes per pulse after the onset of the 1 ms laser pulse during 40 Hz stimulation (red), random stimulation (blue), or no stimulation (black, n = 345,762 40 Hz, 301559 random pulses, and 32,350 randomly selected no stimulation times at least 500 ms apart from 552 40 Hz, 543 random, and 1681 no stimulation periods in four 5XFAD and three WT mice). n, Histogram of the difference in firing rates between 40 Hz stimulation and random stimulation periods shows that both types of stimulation elicit similar amounts of spiking activity (Wilcoxon signed rank test for zero median, P > 0.6, n = 538 stimulation periods from four 5XFAD and three WT mice, NS, not significant). o, Multiunit firing rates per 40 Hz stimulation (red), random stimulation (blue), and no stimulation (black) period for each animal. Box-and-whisker plots show median (white lines in box) and quartiles (top and bottom of box). In all animals firing rates between 40 Hz and random stimulation were not significantly different, showing that the random stimulation condition serves as a control for spiking activity (rank-sum tests for each animal, three WT and four 5XFAD mice, P > 0.09, n = 87, 130, 8, 65, 93, 91, 73 40 Hz stimulation periods and 85, 129, 5, 64, 93, 90, 72 random stimulation periods per animal). We also examined whether 40 Hz stimulation caused neuronal hyperactivity relative to no stimulation, because, according to a recent report, this could have negative effects on neural circuit function26. In most animals the firing rates between 40 Hz or random stimulation and no stimulation were not significantly different (rank-sum tests for each animal, two WT and two 5XFAD, P > 0.25, n = 8, 93, 91, 73 40 Hz stimulation periods and 15, 277, 270, 215 baseline periods per animal) or the firing rates during 40 Hz or random stimulation were lower than during no stimulation (rank-sum tests for each animal, one WT and one 5XFAD, P < 10−5, which is significant when corrected for performing multiple comparisons, n = 130, 65 40 Hz stimulation periods and 379, 187 baseline periods per animal) indicating that 40 Hz stimulation did not cause neuronal hyperactivity. In one animal there was significantly more activity with 40 Hz or random stimulation than during baseline (rank-sum test for one 5XFAD, mouse, P < 10−5, n = 87 40 Hz stimulation periods and 251 baseline periods per animal). Therefore in six out of seven animals we see no evidence that the 40 Hz optogenetic stimulation of FS-PV-interneurons causes hyperactivity.