Deficiency of the transcription factor BMAL1, a core component of the circadian 
clock, results in an accelerated aging phenotype in mice. The circadian clock 
regulates many physiological processes and was recently implicated in control of 
brain-based activities, such as memory formation and the regulation of emotions. 
Aging is accompanied by the decline in brain physiology, particularly decline in 
the response and adaptation to novelty. We investigated the role of the 
circadian clock in exploratory behavior and habituation to novelty using the 
open field paradigm. We found that mice with a deficiency of the circadian 
transcription factor BMAL1 display hyperactivity in novel environments and 
impaired intra- and intersession habituation, indicative of defects in short- 
and long-term memory formation. In contrast, mice double-deficient for the 
circadian proteins CRY1 and CRY2 (repressors of the BMAL1-mediated 
transcription) demonstrate reduced activity and accelerated habituation when 
compared to wild type mice. Mice with mutation in theClock gene (encoding the 
BMAL1 transcription partner) show normal locomotion, but increased rearing 
activity and impaired intersession habituation. BMAL1 is highly expressed in the 
neurons of the hippocampus - a brain region associated with spatial memory 
formation; BMAL1 deficiency disrupts circadian oscillation in gene expression 
and reactive oxygen species homeostasis in the brain, which may be among the 
possible mechanisms involved. Thus, we suggest that the BMAL1:CLOCK activity is 
critical for the proper exploratory and habituation behavior, and that the 
circadian clock prepares organism for a new round of everyday activities through 
optimization of behavioral learning.