(a, b) Effect of BDNF infusion into entorhinal cortex of aged rats on spatial memory in Morris water maze determined by distance (a) and latency (b) measures (P < 0.05 by ANOVA, *P < 0.05 by post hoc Fisher’s test comparing BDNF-treated to aged controls). (c) BDNF effects on search strategy in water maze after platform removal (probe trials) (P < 0.001). (d) Representative samples of search strategy during probe trials in individual rats. (e) Western blot of Erk phosphorylation and Akt phosphorylation (on Ser473, P-S473Akt) in entorhinal cortex of aged cognitively impaired rats compared to young and aged cognitively unimpaired rats; arrow indicates effect of BDNF treatment. Protein loading was standardized to Erk1/2, an abundant cellular protein. (f) Quantification of western blots (P < 0.05 by ANOVA, *P < 0.05 by post hoc Fisher’s test comparing aged cognitively impaired rats and aged cognitively impaired rats treated with vehicle to all other groups). (g) BDNF immunolabeling showing accurate targeting of infusion to entorhinal cortex (*). hpc, hippocampus. Scale bar, 1 mm. (h) Heat maps depicting fold changes of aging-related genes before and after treatment with BDNF. Genes and samples are clustered by similarity; individual columns represent array samples from individual rats compared to young rats.