Mef2c-null mice display altered anxiety-like behavior and decreased cognitive function. (A) The Elevated Plus Maze showed an apparent lowered state of anxiety without loss of function in mice lacking MEF2C compared with controls based on an increase in the percentage of time spent on the open arms but no difference in total arm entries, calculated over a 5-min period. (B) Locomotor activity was not different among null and control groups measured for 30 min as horizontal (locomotion) behavior. (C) Cued and contextual fear conditioning tests revealed that Mef2c-null mice manifest an altered anxiety phenotype, displaying freezing behavior in the altered context before tone onset [t(31) = 2.2, P < 0.05 by ANOVA; n ≥ 10 mice for each paradigm in A–F). Values are mean ± SEM. (D) Total number and order of arm entries on the Y maze were determined in a single 5-min test. (E) Novel object exploration was measured as contact time in one location for four 5-min trials and then a fifth trial with the object moved to a different spatial location. (F) For the paw-clasping observation, mice were suspended by their tails, observed for 10 s, and rated for clasping.