Fig. 4

Abnormal PPR and field IPSP in APP/PS1 mice. a Identical numbers of PV-positive interneurons in the OB of APP/PS1 and WT mice (n = 3 slices/mouse, 3 mice for each genotype). b Representative traces showing evoked GABA current of WT mice in response to puffing brain lysates obtained from WT and APP/PS1 OB, respectively. Each trace represents an average of five sweeps. c Quantification showing similar GABA current density induced by puffing OB supernatant of APP/PS1 and WT mice, indicating total GABA content in the OB did not differ significantly between the two genotypes (n = 13 cells for WT-, and n = 11 for APP/PS1-supernatants). d-e Representative immunoblots and quantification of several GABAergic transporters in the OB. f-g Sample traces of whole-cell patch recording of single eIPSC and quantification showing a significant increase in the amplitude of eIPSCs in APP/PS1 mice (n = 8 cells from 3 WT and 9 cells from 3 APP/PS1, p = 3 × 10^− 7 for interaction of genotype and stimulus strength, two-way ANOVA with Bonferroni’s post-hoc test). h-i Representative traces and quantification of paired-pulse responses. PPR decreased significantly at 100- and 200-ms interpulse intervals (n = 8 cells from 3 WT and 9 cells from 3 APP/PS1; 100 ms: p = 0.004; 200 ms: p = 0.004, one-way ANOVA with Tukey’s post-hoc test). j Similar effect of baclofen on PPR of both groups (n = 11 cells from 5 WT and 8 cells from 3 APP/PS1; 50 ms: p = 0.157; 100 ms: p = 0.006; 200 ms: p = 0.011, one-way ANOVA with Tukey’s post-hoc test). k Diagram showing field EPSP recording in slice. P: periglomerular cell, S: short axon cell. l Representative traces of ONL stimulation induced mixed EPSP (indicated as 1), pure EPSP (2) and IPSP (3). (m-o) Significantly reduced slope of pure EPSP (n = 8 slices from 4 WT and 10 slices from 4 APP/PS1, p = 0.045, two-sample t-test), increased area of IPSP (p = 0.044, two-sample t-test) and reduced E/I ratio (p = 0.003, nonparametric Kolmogorov-Smirnov test). Values represent mean ± SEM. *p < 0.05; **p < 0.01; ***p < 0.001