Stratification of aged rats by cognitive performance. Three independent cohorts of adult (12-13 months) and aged (26-28 months) male Fischer × Brown Norway hybrid (F1) rats were assessed for hippocampus-dependent spatial learning and memory using the Morris water maze. Using mean proximity to the escape platform location as the dependent variable, aged rats performing within the range of adults were classified as cognitively intact, while those with poorer performance were classified as cognitively impaired. Based on this stratification, the performance of both adult and aged intact rats was significantly superior to aged impaired rats in (A) set 1: utilized for preparation of whole-hippocampus synaptosomal fractions used in transcriptomic profiling and mRNA quantitation, (B) set 2: utilized for dissection of CA1, CA3 and DG used in mRNA and protein quantitation, and (C) set 3: perfusion-fixed for immunohistochemical assessments. Points represent individual animals and horizontal bars indicate group means; *** p < 0.001, ANOVA SNK post hoc test. See Table 1 for cohort information. Behavioral data for cohorts 1 and 3 are adapted from reference 27.