Figure 8
A BACE1 inhibitor reverses the pre-plaque LTP deficit (a,b). Three-day treatment with the BACE1 inhibitor LY2886721 transiently restored the ability to induce LTP in 4.5 month-old TG rats. (a) In animals treated with LY2886721 (5 X 0.2 nmol injections i.c.v.), but not with vehicle, 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 vehicle. Insets show representative EPSP traces at the times indicated. Calibration bars: Vertical, 1.0 mV; horizontal, 10 ms. (b) The recovery from the impairment in synaptic plasticity lasted for less than a week in the LY2886721-treated group. The same HFS protocol applied either just before (pre) or one week after (post) the injections of LY2886721 (n = 6) failed to induce either STP or LTP. Data for individual animals are shown in the first two panels and summarized statistically in the bar charts. *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).