Fig. 4

Optogenetic activation of PV interneurons restores AβO_1–42-induced impairment of theta-nested gamma oscillations. a Micro-injection of AAV-CaMKII-ChR2-mCherry and AAV-DIO-C1V1-eYFP virus into CA1 area of PV-Cre mice. b Fluorescence image of ChR2-PC with C1V1-expressing PVs (C1V1-PV). c Experimental schematic. Sinusoidal (5 Hz) blue light (470 nm) and yellow light (590 nm) stimulation for activation of ChR2-PC and C1V1-PV, respectively, and field recording in CA1 area in AβO_1–42-treated slices. d Sinusoidal blue and yellow light stimulation induces theta-nested gamma oscillations as shown in the band-pass filtered LFP (top) and the corresponding spectrogram (bottom), which results in the restoration of gamma oscillations in AβO_1–42-treated slices. e–g Mean PSD (shade indicates SEM) of gamma oscillations (e), mean peak power (f), and mean peak frequency (g) of gamma oscillations in DMSO-treated slice (black), after 20-min treatment of AβO_1–42 in the same slice (red), and with yellow light stimulation of C1V1-PV (yellow) during blue light-induced gamma oscillations. h, i Representative comodulograms showing phase-amplitude coupling of gamma oscillations to theta cycle (h) and mean modulation index (i) in each condition. j–n Schematic illustration of reciprocal PC-PV circuit (j), corresponding phase histogram (k), vector phases and lengths in polar plots (l), mean vector length (m), and circular mean vector phase (n) of CA1 PC’s spike, EPSC in PV, PV’s spike, and IPSC in CA1 PC recorded during gamma oscillations in each condition. One-way repeated-measures (f, g, i), one-way ANOVA with post hoc Tukey’s test (m, ^###p < 0.001, ^##p < 0.01, ^#p < 0.05, ns: not significant), and Watson-Williams test (n, ***p < 0.001, **p < 0.01, *p < 0.05, ns: not significant). Data are represented as mean ± SEM. Data in k–n was collected from the different number of slices (DMSO 23, AβO_1–42 18, AβO_1–42 + C1V1-PV 14) and animals (DMSO 17, AβO_1–42 10, AβO_1–42 + C1V1-PV 8)