Fig. 5: Chronic CP2 treatment improves synaptic activity and LTP in APP/PS1 mice.

a Experimental setting for stimulation-evoked local field potential (LFP) measurement in the hippocampal slice. The stimulation (Stim) electrode was placed at the Schaffer collaterals and the recording (Rec) electrode was placed at the stratum radiatum in the CA1. Scale bar, 200 µm. b Representative raw traces of fEPSP from NTG and APP/PS1 mice. Various stimulation intensities (10–300 µA) were applied to evoke fEPSP. The stimulation pulse width and intervals were fixed at 60 µs and 30 s, respectively. As the stimulation intensity was increased, the initial slope of fEPSP was increased. c CP2 effect on basal synaptic strength. To examine the pre-post synaptic relationships, initial slopes of fEPSP were plotted against amplitudes of presynaptic fiber volleys. Pre-post synaptic relationship in the CP2-treated APP/PS1 group was improved compared to the APP/PS1 group. d Paired-pulse facilitation did not differ between experimental groups. Two stimulations were applied with a short interval to determine presynaptic involvement in synaptic plasticity. e CP2 treatment improves LTP formation. Average traces for fEPSPs in hippocampal slices from each experimental group (n = 2–3 slices from 5 mice per group). Traces represent mean ± S.E.M. per time point. To induce LTP, three tetanic stimulations (100 Hz, 60 µs-pulse width for 1 s) were applied with 3-sec intervals. In APP/PS1 hippocampus, the tetanic stimulation induced early phase post-tetanic potentiation; however, long lasting potentiation was not observed. In the slices from APP/PS1 CP2-treated mice, LTP was induced and maintained over 60 min. NTG, black line; APP/PS1, orange line; NTG + CP2, blue line; APP/PS1 + CP2, red line. f LTP intensities among groups were compared at 60 min (n = 3 slices from 5 mice per group).