Fig. 1.

The mTOR inhibitor rapamycin prevents L-LTP only when applied during induction. fEPSP at Schaffer collateral/commissural fiber-CA1 synapses were simultaneously monitored in two independent pathways (▪, tetanized pathway; ○, untetanized pathway). (A) When rapamycin (1 μM) was transiently (40 min) applied during L-LTP induction, a dramatic decay of fEPSPs was seen (n = 6). A transient rapamycin application 5 min after the delivery of the L-LTP tetanization paradigm (B) or 2 h after completion of the L-LTP induction paradigm (C) did not affect fEPSP slopes (n = 6), nor did a continuous incubation with rapamycin starting 5 min after tetanization (D). (E) L-LTP could be induced after a 40-min rapamycin application and washout, suggesting that the action of rapamycin was reversible. These observations suggest that rapamycin sensitivity of L-LTP is restricted to the induction phase. (F) fEPSP slopes as a percentage of baseline fEPSP in the control untetanized pathway (CONT), untreated tetanized slices (TET), and the conditions displayed in A-E. Measurements of fEPSP slopes taken 240-260 min after completion of the tetanization paradigm. Insets are representative traces of extracellular fEPSPs recorded at the times marked by lowercase letters (^*, different from TET, B, C, D, and E; P < 0.01, NS from CONT).