(A) Dose response to the SHP2 inhibitor on 24-hr memory in non-transgenic flies (2022U). Flies were fed vehicle (0 μM) or varying doses of drug (25, 50, 75 and 100 μM) for eight hours before training, or for eight hours after training (100 μM). * indicates reduced memory performance compared with flies fed with vehicle (0 μM). (B) Effects of eight hours of SHP2 inhibitor 50 μM (inhib [+]) or vehicle (inhib [−]) before training on 24-hr memory in control (OK107;+) and flies overexpressing GOF or wild-type csw. * indicates memory rescue in mutants (D61Y and E76K) after drug feeding (inhib [+]) compared with the same line after vehicle (inhib [−]). (C) MAPK activation in non-transgenic flies treated with SHP2 inhibitor (100 μM) (Inhib [+]) or vehicle (Inhib [−]) after spaced training. * Indicates (Inhib [+]) vs. (Inhib [−]) at 20 min. Bars and data points, mean ± SEM (N=6 in A and B) and (n=3 in C). (D and E) 24-hr memory after 10 trials of spaced training with increasing resting intervals in controls (OK107;+) and flies overexpressing gain-of-function mutant (D61Y and E76K) or wild-type (WT) (D), or expressing a csw mutant with weaker gain-of function effect (I282V) (E). In D and E * indicates higher performance compared with the same fly line when the resting interval of 15 min was used. Bars, means ± SEM (N=8). Asterisks indicate p<0.05.