Fig. 2

Effect of CB1R or TRPV1 receptor blockade on synaptic function and plasticity in 5xFAD/FAAH^−/− mice. Acute slices from 5xFAD/FAAH^−/− mice were preincubated with AM251 [4 µM], AMG9810 [3 µM] or DMSO for 20 min. Drugs or vehicle were added to circulating ACSF during recordings as well. A fEPSPs were recorded from CA3-to-CA1 synapses and normalized to the average baseline value before LTP induction. Left, Time course of fEPSPs before and after theta-burst LTP induction (5 trains of 10 bursts at 5 Hz each, 1 burst = 4 pulses at 100 Hz) from 5xFAD/FAAH^−/− slices treated with AM251 (n = 6 mice), AMG9810 (n = 6 mice), or DMSO (n = 7 mice), using untreated 5xFAD/FAAH^−/− slices as controls (n = 7 mice). Right, Average responses collected from the last 10 min of the recording and normalized to the baseline, with representative traces shown above. Wilcoxon tests revealed significant potentiation in both untreated and treated slices (#p < 0.05). B Input/output curves of fEPSPs evoked at the CA3–CA1 synapse by single pulses of increasing intensities (10–200 µA) in untreated slices (n = 7 mice), and in slices treated with AM251 (n = 7 mice), AMG9810 (n = 7 mice), or DMSO (n = 10 mice) from 5xFAD/FAAH^−/− animals, with representative traces shown on the right. No significant differences among treatment groups were found according to Mann–Whitney tests. For all panels, data are presented as means ± s.e.m