Persistent increased PKMζ in spatial long-term memory. (A) Inset above left, schematic of the active place avoidance training apparatus. The animal is placed on a slowly rotating disk (circle) with a stationary shock zone (red sector), which the animal learns to avoid by attending to cues in the room (square). Inset above right, schematic representation of the 8-trial training protocol with 1-day memory retention testing. Below left, representative 5 min paths. Control animals are placed in the apparatus without conditioning. Below right, mean ± SEM measure of active place avoidance behavior for rats. There is a significant effect of training phase (pretraining, training, retention) (F2,34 = 10.18, P < 0.001), treatment (control and trained) (F1,17 = 10.25, P < 0.01), as well as their interaction (control, n = 8, trained, n = 11, F2,34 = 8.42, P < 0.001). The 1-day retention performance is significantly different (*, Tukey post hoc test, P < 0.01). (B) PKMζ in dorsal hippocampus increases 1 day after 8-trial training. Insets above left, representative immunoblots of PKMζ (Mr = ∼55 kDa); below, mean ± SEM, compared to controls set at 100%. Short-term memory (STM) induced by a single 10 min training session does not increase PKMζ (n’s = 6, t10 = 0.42, P = 0.68). Massed training of eight 10-min sessions, lasting 2.5 h, increases PKMζ by the end of training (n’s = 6, t10 = 2.57, P < 0.05). The increase persists 1 day with retention testing (control, n = 8, trained, n = 10, t16 = 2.13, P < 0.05) and without retention testing (n’s = 8, t14 = 2.62, P < 0.05). The same pattern of unavoidable shocks produces no increase in PKMζ (n’s = 8, t14 = 0.45, P = 0.66). Inset above right, PKMζ protein correlates with 1-day memory strength (100% is mean PKMζ in untrained controls; Spearman’s correlation ρ and P values are given in the figure).