, 2008). Numerous mouse models have also contributed to our understanding of the relationship between circadian disruption and metabolism, with CLOCK mutant mice showing altered basal metabolism and a tendency toward obesity and metabolic dysregulation, while BLU9931 clinical trial normal C57Bl/6 mice housed in a disrupted 10 hr light:10 hr dark cycle show accelerated weight gain and disruptions in metabolic hormones (Karatsoreos et al., 2011 and Turek et al., 2005). Behaviorally, circadian disruption can contribute to cognitive impairments. In a study

of long-recovery versus short-recovery flight crews, it was found that short-recovery crews had impaired performance in a psychomotor task, reacting more slowly and with more errors when compared to a long-recovery crew (Cho, 2001). Furthermore, the above-mentioned mouse model of circadian disruption using a 10:10 L:D cycle shows cognitive inflexibility and shrinkage of dendrites in the medial prefrontal cortex (Karatsoreos et al., 2011). Basal differences in the brain architecture may account for why some individuals are more vulnerable to stress than others. Although trait anxiety behavior varies greatly in human populations, most animal models of anxiety disorders tend to focus on the development of anxiety after a stressful experience. Yet,

when viewed in terms of individual differences, naive adult male Sprague-Dawley and Lewis rats both displayed large variations in baseline anxiety-like behavior in the open field, measured by time spent and distance traveled in the center (Miller et al., 2012). In both I-BET151 cost strains, in spite of the differences in genetic background that exist between them, individuals that fell one SD above (high anxiety) and below (low anxiety) the mean, approximately the top and bottom 15%, had differences

in dendritic length and branching in pyramidal ADAMTS5 neurons from layer II/III of the prelimbic region of the medial prefrontal cortex. In both rat strains, animals in the high-anxiety group had smaller apical dendrites than those in the low-anxiety group, but there was no difference in basal dendrites (Miller et al., 2012). As to the possible origin of these individual differences, it is possible that differences in the early life experience of animals in the breeding facility may be involved. Indeed, studies in animal models show that early life experiences can have a powerful influence on brain development and behavior and the role of maternal care in terms of consistency and quantity, and maternal self-regulation can be considerable (Akers et al., 2008, Meaney and Szyf, 2005, Moriceau and Sullivan, 2006, Parker et al., 2006 and Tang et al., 2012). Prenatal stress and postnatal maternal separation stress are both known to influence prefrontal cortex development and related behavioral responses, particularly after stress in adult life.