(A) Permissive levels of tPA restore ocular dominance plasticity. Short-term MD during the critical period slightly reduces CBI values in tPA Het from non-MD levels (0.64 ± 0.02 and 0.77 ± 0.02, respectively) but does not reach WT levels (shaded zone; P < 0.001, Student's t test vs. STMD for WT in Fig. 3A) and is no better than tPA KO levels (P = 0.5 vs. STMD for KO in Fig. 3A). With long-term MD, CBI values in tPA Het (0.53 ± 0.07) are significantly reduced from brief MD and tPA KO (P < 0.001 vs. LTMD for KO in Fig. 3A). Late MD effects in tPA Het (late-LTMD at P60; 0.66 ± 0.05) are negligible in postcritical period adult animals similar to WT (CBI = 0.65 ± 0.07, n = 4; P = 0.8). (B) Monocular TTX injections (4 days) during the critical period significantly reduce CBIs in tPA Het compared with brief MD (P < 0.01 vs. STMD for Het in A), but remain weaker than in WT mice (CBI = 0.54 ± 0.05 and 0.39 ± 0.10, Het vs. WT). Note monocular TTX produces more powerful plasticity than eyelid suture (shaded zone) in WT animals (18). (C) Direct intracranial infusion of recombinant tPA during 1-wk MD (7 days from P25–26) restores plasticity to tPA KO mice. No gross abnormalities were observed after tPA injections (not shown). (CBI = 0.44 ± 0.02, 0.69 ± 0.01, and 0.54 ± 0.01 for WT, vehicle KO, and tPA KO, respectively). *, P < 0.05; **, P < 0.01; ***, P < 0.005, Student's t test.