Figure 1.
Cholinergic agonist-induced enhancement of LTP is blocked and reversed in PS1 mutant knockin mice. A. Slices were perfused for 30 min with 50 μM carbachol (Carb) and wash out for 20 min. B and C. Plots of the normalized initial EPSP slope. Following a 10 minute period of baseline recording, high frequency stimulation (HFS; 100 Hz, 1 s) was applied at CA1 stratum radiatum. Slices were incubated for 60 minutes and perfused with 50 μM carbachol or vehicle (control) during the recording. In slices from wild-type (WT) mice, HFS induced a normal LTP and the LTP was significantly enhanced by carbachol. In slices from PS1KI mice, LTP was reduced in the presence of carbachol. Values are the mean and SEM (6-10 slices from 5 or 6 mice). *p< 0.05, **p< 0.01, compared to the control value. D. I-V curves of AMPA and NMDA currents generated from whole-cell patch clamp recordings in slices from WT and PS1KI mice treated with either vehicle or carbachol. Currents were generated by a series voltage steps from −60 mV to +60 mV. The NMDA current (induced at positive holding potentials) was decreased in neurons from PS1KI mice compared to WT mice, **p< 0.01.