Increasing the strength of the conditioning stimulation protocol overcame the inhibition of LTP in pre-plaque freely behaving TG rats. (a) At 5–6 months of age the standard 200 Hz conditioning stimulation (arrow) triggered robust LTP in WT rats but failed to induce significant STP or LTP in TG rats. (b) Repeated high-intensity 400 Hz tetanization (strong HFS, large arrow head) in 5–6 month-old animals induced similar magnitude LTP in TG and WT rats. Time-course graphs are shown in the left hand panels with summary statistics for STP (first 10 min post-HFS) and LTP (last 10 min post-HFS) shown in the right hand panels. Insets show representative EPSP traces at the times indicated. Calibration bars: Vertical, 1.0 mV; horizontal, 10 ms. Values are the mean ± S.E.M. % pre-HFS baseline EPSP amplitude. *P < 0.05 compared with WT littermates.