Fig. 3
AβO1–42 causes synapse-specific dysfunction of PV-to-PC synapses, but not SST-to-PC synapses. a Experimental schematic. Whole-cell voltage-clamp recordings in CA1 PC (top) and representative IPSCs (bottom) during blue light-induced gamma oscillations in DMSO-treated (black), AβO1–42-treated slices (red), and DMSO-treated slice with GABAzine (gray). b, c Micro-injection of AAV-CaMKII-ChR2-mCherry and AAV-DIO-Arch-eYFP into CA1 area (top) and fluorescence image (bottom) of ChR2-expressing PCs (ChR2-PC) with Arch-expressing PV interneurons (Arch-PV) in PV-Cre mice (b) and ChR2-PC with Arch-expressing SST interneurons (Arch-SST) in SST-Cre mice (c). d, e Same as a but with inactivation of Arch-PV (d) and Arch-SST (e) using tonic yellow light (590 nm) stimulation in DMSO- and AβO1–42-treated slice. f, g Mean IPSC frequency (f) and mean IPSC amplitude (g) in each condition. h Micro-injection of AAV-DIO-ChR2-mCherry into CA1 area of PV-Cre mice (top) and fluorescence image (bottom) of ChR2-expressing PV interneurons (ChR2-PV). i, j Experimental schematic. Whole-cell voltage-clamp recordings in CA1 PC (i) to record PV-evoked IPSCs (j, left) and stimulus-response (S-R) curve (j, right) in response to different light stimulation powers. k, l Representative PV-evoked IPSCs in CA1 PC in response to light stimulation (10 pulses, 50 Hz, k, left), paired-pulse ratio (PPR) of the 2nd IPSC/1st IPSC (k, right), total IPSC charge (l, left), and IPSCs normalized to the 1st IPSC to show short-term plasticity (l, right) in DMSO-treated (filled circles) and AβO1–42-treated slices (empty circles). m–q Same as h–l but by activating ChR2-expressing SST interneurons (ChR2-SST) for SST-evoked IPSCs in SST-Cre mice. Unpaired Student’s t test (k, l (left), p, q (left), **p < 0.01, *p < 0.05, ns: not significant), one-way (f, g, ###p < 0.001, ##p < 0.01, ns: not significant) and two-way ANOVA with post hoc Tukey’s test (j, l (right), o, q (right), ###p < 0.001, #p < 0.05, ns: not significant). Data are represented as mean ± SEM