Figure 3.

Ifenprodil rescues Tat-induced learning deficits. A, Schematic illustrating the timing of surgical cannula implantation, ifenprodil or saline administration (injection), and training and testing of context and trace (CS) fear conditioning relative to ICV vehicle or Tat infusion. Inset, Training scheme showing 120 s baseline, then 2 CS–US pairings (30 s CS, 30 s trace interval, and 2 s US), followed by a 60 s posttraining period. B, Diagram of coronal mouse brain illustrating placement of chronic indwelling guide cannula directed at lateral ventricle and infusion cannula used to administer Tat or vehicle. C, D and F, G, Bar graphs showing percentage freezing in context test (CTX) altered context test (A) and conditioned stimulus test (CS) for subject groups that received PBS (2 μl ICV) followed by intraperitoneal saline on days 7 and 8 (control), PBS then 10 mg/kg ifenprodil intraperitoneally (ifen), Tat (100 ng ICV) then saline (Tat) and Tat then ifenprodil (Tat + ifen). C, Infusion of Tat induced deficits in contextual and trace-cued fear conditioning. Ifenprodil rescued learning in mice treated with Tat, but had no effect on its own. D, Mice were retested 28 d later at a remote time point (days 39 and 40). n = 10 in all groups (C,D). All data are shown as mean ± SEM. *Significant difference from control. †Significant difference from all other treatment conditions. E, Diagram of timeline of shifted experiment. Training was shifted to after transient rescue of spine density by ifenprodil (day 11; Fig. 2B). F, Mice trained on day 11 (3 d after administration of ifenprodil or saline) showed deficits in contextual and trace-cued learning; ifenprodil failed to rescue cognitive function. G, Retesting 28 d later showed the same pattern of effects, a Tat-infusion induced deficit in contextual and trace-cued fear, but no effects of ifenprodil administration. n = 7 in groups treated with saline and n = 5 in groups treated with ifenprodil. All data are mean ± SEM. #Significant effect of Tat infusion.