A γ-secretase inhibitor reverses the pre-plaque LTP deficit (a,b). Three-day treatment with the γ-secretase inhibitor MRK-560 transiently restored the ability to induce LTP in 5 month-old TG rats. (a) In animals treated with MRK-560 (5 X 0.19 nmol injections i.c.v.) HFS triggered robust STP and LTP that was stable for at least 3 h. Left hand panel shows the time course of synaptic plasticity. Summary bar chart of STP and LTP in left hand panel. *P < 0.05 compared with pretreatment levels of potentiation in the same animals (pre). Insets show representative EPSP traces at the times indicated. Calibration bars: Vertical, 1.0 mV; horizontal, 10 ms. (b) Data for individual animals pre-, during and one week post-treatment with MRK-560 are shown in the two panels. *P < 0.05 compared with pre. Values are the mean ± S.E.M. % pre-HFS baseline EPSP amplitude at 10 min (STP) or 3 h (LTP).