RyR priming enables establishment of STC in APP/PS1 mice. (A) Control experiments showing STC induced by a strong-before-weak protocol in WT mice. Induction of L-LTP by STET in S1 (filled circles) was followed by E-LTP induced by WTET (single arrow) in S2 (open circles). Here E-LTP was transformed into an L-LTP, showing STC (n = 7). (B) Experimental design was similar to A, but STC was induced in APP/PS1 mice and potentiation of both synaptic inputs S1 (filled circles) and S2 (open circles) returned to baseline levels within 180 min, showing impaired STC (n = 8). (C) As in B, except that RYA (10 µM) was bath-applied for 30 min and then washed out for 30 min. Here L-LTP in S1 was rescued (filled circles) and E-LTP in S2 was transformed into L-LTP in S2 (open circles), expressing STC (n = 7). (D) Bar graph showing differences in the level of potentiation of synaptic input S1 and S2 after the induction of L-LTP or E-LTP, respectively, at 240 min between the three different conditions presented in A–C. Asterisks indicate significant group differences in potentiation (*P < 0.05 and **P < 0.01). Symbols/traces are as in Fig. 1.