Pre-plaque disruption of hippocampal LTP induction in freely behaving TG rats in vivo (a,b). In freely behaving chronically implanted rats, LTP at CA3-to-CA1 synapses in the stratum radiatum was strongly impaired in 4 but not 3 month-old McGill-Thy1-APP-TG rats. (a) At 3 months of age application of a standard 200 Hz conditioning stimulation protocol (standard HFS, arrow) induced robust LTP that persisted for at least 3 h in both WT and TG rats. (b) In contrast, at 4 months of age, whereas the same conditioning stimulation triggered robust LTP in WT rats, the protocol only triggered a weak, non-significant, STP in TG 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.